Wetenschapssymposium. Programma en abstracts. MCL academie 15 maart 2016

Wetenschaps- symposium MCL academie | 15 maart 2016

Programma en abstracts

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Inhoudsopgave

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Voorwoord

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Programma

Abstracts

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Voorwoord Het wetenschapssymposium, al weer de achtste editie! Een moment om met elkaar terug en vooruit te blikken op wetenschappelijk onderzoek in het MCL. Het MCL heeft een stevige ambitie; tot de top behoren van de Nederlandse ziekenhuizen. Wetenschappelijk onderzoek speelt daarbij een onmisbare rol. Het gaat hand-in-hand met het leveren van topzorg. Met wetenschappelijk onderzoek willen we bijdragen aan “state of the art” patiëntenzorg. In dit programmaboekje kunt u lezen dat hierin binnen het MCL belangrijke en goede stappen worden gezet. Onderzoek leeft in het MCL, het doet ertoe. Dit geldt over de volle breedte van het ziekenhuis. Niet alleen de kwantiteit, een verdubbeling van het aantal ingestuurde abstracts ten opzichte van vorige jaar, maar zeker ook de kwaliteit van het onderzoek laat dit zien. En daardoor wordt het ieder jaar moeilijker om het programma vast te stellen. Moeilijk, omdat het programma onvoldoende ruimte biedt om al het goede onderzoek volledig voor het voetlicht te brengen. Je zou ook kunnen zeggen, dat is goed nieuws. In het verlengde hiervan introduceert de wetenschapscommissie een nieuw onderdeel op het programma; power talks. Tien onderzoekers die ieder – in een race tegen de klok van 3 minuten – laten zien hoe hoog de kwaliteit van onderzoek binnen het MCL is. En er kan er maar 1 de beste zijn. De keuze is aan u (houdt uw smartphone bij de hand!). Daarnaast kent het Wetenschapssymposium natuurlijk de vaste onderdelen. De W.K. Brouwerprijs voor de beste klinisch les en de Auletiusprijs voor het beste wetenschappelijk onderzoek worden traditiegetrouw uitgereikt. Vier kandidaten presenteren hun onderzoek breeduit. Voor drie daarvan is dit een onderdeel van lopend promotieonderzoek. Twee andere MCL-promovendi hebben hun proefschrift vorig jaar succesvol verdedigd. Zij vertellen ons over hun onderzoek, waarom dit belangrijk was en hoe het is om binnen het MCL promotieonderzoek te doen. Last but not least neemt Kees Donkervoort ons mee in de ambitie van het MCL om zich verder te profileren als STZ ziekenhuis, waarbij onderzoek hand-in-hand gaat met het leveren van topzorg. Verder nog verrassingen? Kom op tijd, want u wilt het begin niet missen! Rest mij om u een leerzaam en vooral inspirerend symposium toe te wensen! Nic Veeger Hoofd Wetenschapsbureau MCL Academie, Voorzitter wetenschapscommissie MCL Leeuwarden, 9 maart 2016

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Programma

MCLWetenschapssymposium Dinsdag 15 maart 2016 Dagvoorzitter dr. Mels Hoogendoorn

16:00 – 16:25 uur

Ontvangst

16:25 – 16:30 uur

Opening

16:30 – 16:45 uur “What can be the effect on PROMs of spiritual care training to hospital staff in the Netherlands? (SPIRIT-NL).” Spreker: Drs. Joep de Geer, onderzoeker SPIRIT-NL Geestelijk Verzorger Ziekenhuiszorg, Afdeling Geestelijk Verzorging, Medisch Centrum Leeuwarden.

16:45 – 17:00 uur “The role of initial clinical presentation, comorbidity and treatment in multiple myeloma patients on survival: a population-based study.” Spreker: Drs. Berdien Oortgiesen, onderzoeker hemato-oncologie, Ziekenhuisfarmacie, Medisch Centrum Leeuwarden.

17:00 – 17:15 uur “Improving outcomes of patients with Alzheimer’s disease: long-term disease course and nutritional status in a ‘real-life’ setting.” Spreker: Dr. Erika Hiemstra-Droogsma, AIOS Klinische Geriatrie, Medisch Centrum Leeuwarden. (promotieonderzoek 23 november 2015).

17:15 – 17:30 uur “Visie op en structurering van het medisch wetenschappelijk onderzoek binnen het MCL.” Spreker: Drs. Kees Donkervoort, voorzitter directie MCL.

17:30 – 18:00 uur

Power talks - 5 short research presentations

18:00 – 18:45 uur

Pauze met buffet

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Vervolg programma MCL Wetenschapssymposium Dinsdag 15 maart 2016 18:45 – 19:15 uur

Power talks - 5 short research presentations

19:15 – 19:25 uur “Een patiënt met hyponatriaemie als uiting van acute bijnierschorsinsufficiëntie” Spreker: Drs. I.T. Bootsma, semi-arts MCL, Beste Klinische Les 2015.

19:25 – 19:40 uur “The Safety of Bridging in Elective Gastrointestinal Endoscopic Procedures, results from a population based cohort.” Spreker: Drs. Fimke Heslinga, semi-arts, interne geneeskunde, Medisch Centrum Leeuwarden.

19:40 – 19:55 uur “A one-day-visit program in a specialised severe asthma centre improves asthma control, quality of life and healtcare utilisation.” Spreker: Drs. Akke-Nynke van der Meer, AIOS, Centrum voor longziekten, Medisch Centrum Leeuwarden.

19:55 – 20:10 uur “18F-FDG PET-CT in Fever and Inflammation of Unknown Origin.” Spreker: Dr. Hans Balink, Nucleair Geneeskundige, Nucleair Geneeskunde, Medisch Centrum Leeuwarden. (promotie onderzoek 20 februari 2015).

20:10 – 20:20 uur

Publieksstemming “Beste short research presentations - Power talks”.

20:20 – 20:30 uur

Prijsuitreiking WK Brouwerprijs voor beste klinische les, en Auletiusprijs voor beste wetenschappelijk onderzoek 2015.

20:30 – 21:30 uur Afsluiting symposium Borrel en hapjes, met toast op winnaars Auletiusprijs en WK Brouwerprijs.

Aankondiging Wetenschapssymposium 2017: dinsdag 14 maart 2017; deadline abstracts 2 januari 2017.

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Power Talks – Short research presentations 1)

Hoeveel patiënten zijn ondervoed bij opname op de Intensive Care. Hanneke Buter, Intensive Care, Medisch Centrum Leeuwarden, Leeuwarden.

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Effect of gastric bypass on the bioavailability of metoprolol from immediate and controlled-release tablets: a single oral dose study. JP Yska, ziekenhuisapotheker, Dept of Clin Pharmacy and Clin Pharmacology, MCL, Leeuwarden.

3) Right ventricular function after cardiac surgery is a strong independent predictor for long term mortality. I.T. Bootsma, Intensive Care, Medisch Centrum Leeuwarden, Leeuwarden. 4)

Disease and treatment characteristics in patients with newly diagnosed Polycytemia Vera: A Detailed Population-Based Study. Wustman T, Department of Hematology, Medisch Centrum Leeuwarden, Leeuwarden.

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A Comparison Between the Metronome-Paced Tachypnea Test and Cardiopulmonary Exercise Testing in Detecting Dynamic Hyperinflation in an Average COPD Population. E. Vis1 Department of pulmonology, Medical Centre Leeuwarden, Leeuwarden.

Pauze 6) Clinical, ultrasound and radiographic evaluation of hip joints in ankylosing spondylitis patients with active disease. F.R.Wink. Rheumatology, Medical Center Leeuwarden, Leeuwarden. 7) Strooistraling afkomstig van de Mini C-boog tijdens hand-/pols operaties. Juliaan van Rappard. Afdeling Plastische Chirurgie, Medisch Centrum Leeuwarden, Leeuwarden. 8)

Vriescoupe-gecontroleerde excisie van huidmaligniteiten in het gelaat; analyse van de betrouwbaarheid en het klinische beloop. Kor H. Hutting. Afdeling Plastische chirurgie en handchirurgie, Medisch Centrum Leeuwarden, Leeuwarden.

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Conventional CABG or On Pump Beating Heart: a difference in myocardial injury? Kornelis J. Koopmans Department of Extracorporeal Circulation, Medical Center Leeuwarden, Leeuwarden.

10) When to activate a multidisciplinary team for an acute abdominal aortic aneurism? M. Maltha Department of Emergency Medicine, Medical Centre Leeuwarden, Leeuwarden.

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Abstract 1 - selected for oral presentation What can be the effect on PROMs of spiritual care training to hospital staff in the Netherlands? (SPIRIT-NL) van de Geer, Joep (1), Zock, Hetty (2), Leget, Carlo (3), Andela, Richtsje (4), Prins, Jelle (4), Veeger, Nic (4), Groot, Marieke (5.), Vissers, Kris (5). (1) Chaplaincy/palliative care, Medical Centre Leeuwarden, Leeuwarden, Netherlands (2) University of Groningen, Groningen, Netherlands (3) University of Humanistic Studies, Utrecht, Netherlands (4) MCL Academy, Medical Centre Leeuwarden, Leeuwarden, Netherlands (5) palliative care, Radboud UMC, Nijmegen, Netherlands

Background Spirituality is reported as important for palliative patients. There is an increasing demand for spiritual care training. In a multicentre trial, healthcare chaplains of 7 non academic teaching hospitals implemented a pilot training (SC) in palliative care (PC) to 9 multidisciplinary clinical teams on regular curative departments where also palliative patients receive treatment. Aim Measuring the effect of the intervention training SC on the perceived care and treatment as experienced by patients. Assessment of the spiritual needs and attitudes of hospitalized palliative patients in the Netherlands. Methods In an explorative multicentre trial, we have collected data of 85 palliative patients on pilot and control departments, pre and post intervention, using questionnaires on physical symptoms, spiritual distress and the perceived focus of caregivers on their spiritual needs, quest for meaning or existential questions, spiritual involvement and attitudes (SAIL), followed by a single open question ‘how was it for you to fill in the questionnaire?’. Quantitative and qualitative methods were used to analyse the effects of the intervention. Results All patients scored highly on spiritual themes and involvement. They reported attention to their spiritual needs as highly important. No significant effect of training staff on spiritual distress of patients and proxies was measured. There was a significant effect on the attention to spiritual and existential needs that patients experienced, and a possible effect on patients’ sleeping. Half of the patients reported a degree of reflection on spiritual or existential questions as a result of filling in the questionnaire.

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Conclusions Training spiritual care can be measured in patient reported outcome measures and seems to have a positive effect on the quality of care. Further research should focus on how to optimize training spiritual care for hospital staff so that an effect on spiritual distress is possible.

Abstract 2 - selected for oral presentation The role of initial clinical presentation, comorbidity and treatment in multiple myeloma patients on survival: a population-based study. B. E. Oortgiesen (1), E.N. Van Roon (1), P. Joosten (2), R.E. Kibbelaar (3), H. Storm (4), S. Hovenga (2), B. Van Rees (2), G. Woolthuis (2), N. Veeger (5), E.G. De Waal (2), M. Hoogendoorn (2). (1) Department of Clinical Pharmacy & Pharmacology, MCL, Leeuwarden (2) Department of Haematology, MCL, Leeuwarden; Nij Smellinghe, Drachten, Antonius, Sneek, Tjongerschans, Heerenveen (3) Department of Pathology, Pathology Friesland, Leeuwarden (4) Department of Clinical Chemistry, MCL CERTE (5) Department of Epidemiology, MCL Academy, Leeuwarden

Background Population-based studies in unselected multiple myeloma (MM) patients in the era of novel agents are relatively limited. Explanations for the notable variation in prognosis across patients may in part be explained by the heterogeneity at initial clinical presentation, the pre-existing comorbidities, disease biology and response to the therapy. Specific end-organ damage caused by the disease, such as hypercalcaemia, renal failure, anaemia and bone lesions known as the CRAB symptoms may be associated with worse prognosis in the elderly MM patients. Aim This prospective, observational population-based cohort study was performed to determine overall survival (OS) in MM patients in Friesland, the Netherlands in the era of novel agents and to analyse the influence of first-line treatment, MM-related end-organ damage and comorbidities at initial presentation on OS. Methods Detailed clinical information was obtained from the population-based registry ‘HemoBase’ during the period January 2005 to January 2013, with a follow-up to January 2014. The primary end-point was OS, defined as time of diagnosis until death by any cause. Survival curves were calculated according to Kaplan-Meier.

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Results Of all MM patients, 83% were symptomatic with a median OS of 40 months. In the age categories <65, 65-75 and ≥75 years, 99%, 94% and 87% of the patients received treatment, with a median OS of 92, 42 and 31 months respectively. OS for patients with or without treatment was 43 and 3 months respectively. In multivariable analysis, increasing age was an independent risk factor for worse OS (<65: reference; 65–75: HRadj. = 2.2.(95% CI 1.3–3.7) and ≥75: HRadj. = 2.8 (95% CI 1.7–4.8); P < 0.001). Not receiving initial treatment, hypercalcaemia and impaired renal function at initial presentation were independent risk factors for worse OS (HRadj. = 4.0 (95% CI 2.1–7.7); P < 0.001, HRadj. = 1.7 (95% CI 1.2–2.6); P = 0.006 and HRadj. = 2.6 (95% CI 1.7–4.0); P < 0.001, respectively). Comorbidity according to CCI score was not an independent variable predicting OS. Conclusions In this detailed population-based study of a complete Dutch cohort of unselected symptomatic MM patients a median OS of 40 months was observed. Not receiving first-line treatment, increasing age, hypercalcaemia and impaired renal function, but not the CCI score at initial presentation were significantly associated to worse median OS.

Abstract 3 - selected for oral presentation The Safety of Bridging in Elective Gastrointestinal Endoscopic Procedures, results from a population based cohort. F.A. Heslinga (1), BSC; N.J.G.M. Veeger (1,2), PhD ; L.M. Geven (1), MD.; M. Hoogendoorn (1), MD PhD. (1) Medical Center Leeuwarden (2) University of Groningen, University Medical Center Groningen, the Netherlands

Background When patients treated with vitamin K antagonists (VKA) undergo an elective invasive procedure, interruption of the anticoagulant treatment must be considered to prevent bleeding complications. In patients undergoing a gastrointestinal (GI) endoscopy, anticoagulation increases the risk of a major GI bleed. However, by stopping VKA, the thrombosis risk can be increased. To minimize the risk of thrombosis, bridging therapy is often provided in “high stroke risk” patients. Aim The present single-center observational study aims to evaluated the safety of bridging in high stroke risk patients undergoing elective GI endoscopy.

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Methods Over a the period of April 2009 to April 2014, 239 “higher stroke risk” patients received a perioperative bridging strategy in accordance with the local bridging protocol and 125 patients with a lower a priori stroke risk in whom no bridging was applied. In the bridging protocol a perioperative bridging strategy was proposed for patients with atrial fibrillation and CHADSVasc score > 4, and /or patients with mechanical heart valves or a recent history of venous thromboembolism. In patients with lower stroke risk bridging was not applied. The primary endpoint was periscopic major bleeding, secondary endpoints were thromboembolic complications and all clinically relevant bleeds within 30 days after endoscopy. Definitions were according to the International Scientific and Standardization Committee guidelines. Results Groups were comparable except for the a priori stroke risk related variables. With respect to major bleeding, 3.3% versus 2.4% resulted in an adjusted odds ratio (OR) of 1.4.(95% CI 0.36 to 5..6, p=0.62), for bridging compared to non-bridging. Clinically relevant bleeds had occurred in 6.7% versus 4.0%, adjusted OR=1.7 (95% CI 0.61 to 5..0, p=0.30). For major bleeding (OR =10.2.(95%CI 2.2 to 48.1, p=0.003) as well as for all clinically relevant bleeds (OR=4.3.(95% CI 1.7 to 11.0, p=0.003) performing a polypectomy was the main determinant for major bleeding. In all patients, only 1 stroke was observed in the bridging group (0.4%). Conclusions Our analysis of a population-based 5.-year cohort of patients on VKA, who underwent a GI-endoscopic procedure showed no significant difference in major bleeding between bridged patients and non-bridged patients. Although our study was a non-randomized study, it does give a reflection of the real world and illustrates that bridging strategies in patients at high risk for thromboembolism appears to be safe.

Abstract 4 - selected for oral presentation A one-day-visit program in a specialised severe asthma centre improves asthma control, quality of life and healtcare utilisation. A.N. van der Meer (1), H. Pasma (1), W. Kempenaar (1), J. Pelinck (2), M. Schutten (3), H. Storm (4), A. ten Brinke (1). (1) Department of pulmonology (2) Department of psychology (3) Department of physiotherapy (4) Department of clinical chemistry, Medical Centre Leeuwarden, Leeuwarden, Netherlands

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Background Patients with uncontrolled asthma report ongoing symptoms, poor quality of life and extensive healthcare utilisation and might benefit from management by a specialised severe asthma team. However, it is unknown whether a one-time evaluation and advice from asthma experts, without long-term supervision, provides favourable outcomes. Aim We prospectively evaluated asthma control (ACQ), quality of life (AQLQ) and healthcare utilisation (HCU) before and 1 year after a one-day-visit program in a specialised severe asthma centre, including a systematic multidisciplinary assessment resulting in a personalised management plan to be implemented by patients own pulmonologists. In addition, we analyzed whether specific characteristics could predict a better outcome. Methods 40 uncontrolled asthma patients with baseline assessments between June 2013-June 2014 completed questionnaires (ACQ, AQLQ, HCU) at baseline and 6 and 12 months follow-up. Results ACQ improved from 2.6 (IQR 1.7-3.2) at baseline to 1.8 (1.2-3.2) at 1 year (p=0.003). AQLQ improved from 4.8 (4.0-5..2) to 5..3.(4.4-6.0) (p<0.001). At follow-up there was a reduction in patients with ≥2 exacerbations (95% versus 17%, p<0.001), ≥1 emergency room visit (78% versus 37%, p<0.001) or ≥1 hospitalisation (47% versus 10%, p=0.001). We found no changes in maintenance prednisolone dose. Asthma outcomes were not dependent on gender, smoking history or phenotype. Improvement in ACQ was related to higher 6MWD (r=-0.40, p=0.01), lower BMI (r= 0.34, p=0.03) and higher levels of sputum eosinophils (r=-0.41, p=0.05) at baseline. Reduction of exacerbations to higher levels of NO (r=-0.34, p=0.03), and eosinophils in blood (r=-0.32, p=0.04) as well as in sputum (r=-0.43, p=0.04). Conclusions Evaluation of patients with uncontrolled asthma in a one-day-visit program in a specialised severe asthma centre was associated with clinically significant improvements in asthma control, quality of life and healthcare utilisation after 1 year. This one-day-visit approach seems beneficial for a large group of patients with uncontrolled asthma and might reduce the number of patients that depend on expensive treatment modalities and continuous management in a specialised centre.

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Abstract 5 - selected for short Power talk Hoeveel patiënten zijn ondervoed bij opname op de Intensive Care. Hanneke Buter, Marja van der Bijl, Fleurine Meppelink, Anja van Wieren en Matty Koopmans. Intensive Care, Medisch Centrum Leeuwarden, Leeuwarden.

Achtergrond Ondervoeding leidt tot een toegenomen morbiditeit en mortaliteit tijdens opname in het ziekenhuis. Volgens de Landelijke Prevalentie Zorgproblemen 2014 is 14% van alle patiënten in algemene ziekenhuizen ondervoed. In studies van patiënten op de Intensive Care varieert het percentage ondervoeding van 22 tot 65%. Voor het screenen op ondervoeding gebruiken we in het MCL de SNAQ score, dit is een vragenlijst gecombineerd met de BMI. De voedingstoestand kan ook worden gemeten middels bioelektrische impedantie vector analyse (BIVA) waarmee uit de lichaamsresistentie en -reactance de fase hoek kan worden berekend. De fase hoek weerspiegelt de integriteit van de celmembraan en geeft de verdeling van water tussen de intracellulaire en de extracellulaire ruimte weer. Een normale fase hoek is gedefinieerd als > 5° bij mannen en > 4.6° bij vrouwen; bij een lagere waarde wordt verondersteld dat er sprake is van ondervoeding. Doel Het bepalen van het percentage patiënten dat ondervoed is bij opname op de Intensive Care, gemeten met de SNAQ score en de BIVA. Methode In de periode september t/m november 2015 is bij opeenvolgende patiënten die werden opgenomen op de IC binnen 24 uur na opname een BIVA meting verricht. Van deze patiënten werden de demografische gegevens verzameld en de SNAQ score gecontroleerd. Resultaten 132 patiënten werden geïncludeerd, 42 na acute en 90 na electieve opname. De gemiddelde leeftijd was 67 (± 12) jaar, 66 % was man. De BMI bedroeg 27 (± 4). De APACHE IV score was 58 (± 24). Met de SNAQ score werd bij 13,6 % van de patiënten ondervoeding vastgesteld (14 % van de acute en 13 % van de electieve opnames). Met de BIVA bedroeg het percentage ondervoeding 34 %, (50 % van de acute en 27 % van de electieve opnames). Middels lineaire regressie werd een significante relatie tussen SNAQ en de fase hoek aangetoond (p=0.007). Er bestond geen relatie tussen de BMI en de fase hoek.

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Conclusie Ondervoeding kwam voor bij 13,6 % volgens de SNAQ en bij 34 %, gemeten met de BIVA, van de patiënten die werden opgenomen op de IC. Mede gezien de correlatie tussen beide meetmethoden lijkt de BIVA een gevoeliger methode om ondervoeding vast te stellen dan de SNAQ score. Het eerder onderkennen van ondervoeding bij patiënten die een electieve ingreep moeten ondergaan geeft de mogelijkheid de zorg in het preoperatieve traject te verbeteren.

Abstract 6 - selected for short Power talk Effect of gastric bypass on the bioavailability of metoprolol from immediate and controlled-release tablets: a single oral dose study. J.P. Yska (1), J Wanders (1), B. Odigie (1), E.C. Boerma (2), F.L. Ubels (3), J.A. Apers (4), M. Emous (4), E.R.E. Totté (4), B. Wilffert (5,6), E.N. van Roon (1,5). (1) Dept of Clin Pharmacy and Clin Pharmacology, MCL, Leeuwarden (2) Dept of Intensive Care, MCL, Leeuwarden (3) Dept of Internal Medicine, MCL, Leeuwarden (4) Dept of Surgery, MCL, Leeuwarden (5) Unit of Pharmacotherapy and Pharmaceutical Care, Dept of Pharmacy, University of Groningen, Groningen (6) Dept of Clin Pharmacy and Pharmacology, University Medical Center Groningen, Groningen

Background Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), induces changes in the gastrointestinal tract that theoretically might alter the pharmacokinetics of drugs. However, results from pharmacokinetic studies are sparse. Aim To investigate the effect of RYGB on the bioavailability of metoprolol and its metabolite α-OH metoprolol after a single oral dose of metoprolol immediate (IR) and controlled release (CR) tablet in female bariatric surgery patient volunteers before and after surgery. Methods An explorative two phase single oral dose pharmacokinetic study of metoprolol under fasting conditions in female patients undergoing RYGB. The dose was administered twice in each patient, 1 month before and 6 months after surgery. After intake of 100 mg of metoprolol IR or CR tablet 11 blood samples were collected at 0, 0.5., 1, 1.5. (only IR), 2, 3, 4, 5., 6, 8, 10 and 24 (only CR) hour. Concentrations were determined by means of a validated LC-MS method. Blood pressure and heart rate were regularly monitored. Parameters to be determined before and after surgery were Cmax, Tmax, and AUC0-10 (IR) or AUC0-24 (CR) of metoprolol and α-OH metoprolol. The main endpoint was the ratio of AUCafter/AUCbefore of metoprolol and α-OH metoprolol.

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Results Seven patients were included in the metoprolol IR part of the study (mean age (SD): 37±8 year; mean BMI (SD) before surgery: 39.9±2.1 kg/m², 6 months after surgery: 30.8±2.3 kg/m²). After intake of metoprolol IR tablet large inter- an intraindividual differences for AUC of metoprolol before and after surgery were observed (range ratio AUCafter/before: 0.74-1.98). For α-OH metoprolol ratios of AUCafter/before ranged from 1.05 to 1.36. Five patients were included in the metoprolol CR part of the study (mean age (SD): 37±5 year; mean BMI (SD) before surgery: 38.6±4.0 kg/m², 6 months after surgery: 29.5±4.3 kg/m²). After intake of metoprolol CR tablet a reduction in bioavailability of metoprolol was observed (range ratio AUCafter/before: 0.43-0.77). For α-OH metoprolol ratios of AUCafter/before ranged from 0.74 to 0.98. Conclusions RYGB may influence the bioavailability of metoprolol from an IR tablet. After RYGB clinicians may consider to adjust the dose according to clinical response. RYGB reduces the bioavailability of metoprolol from a CR tablet. After RYGB clinicians may consider to increase the dose or switch to IR formulation according to clinical response.

Abstract 7 - selected for short Power talk Right ventricular function after cardiac surgery is a strong independent predictor for long term mortality. I.T. Bootsma, MD (1), F. de Lange, MD PhD (1,2), M. Koopmans MSc (1), J. Haenen, MD (2), P.W. Boonstra, MD PhD (3), T. Symersky, MD (4), E.C. Boerma, MD PhD (1). (1) Medical Centre Leeuwarden, Department of Intensive Care, Leeuwarden (2) Medical Centre Leeuwarden, Department of Cardiothoracic Anaesthesiology, Leeuwarden (3) Medical Centre Leeuwarden, Department of Cardiothoracic Surgery, Leeuwarden (4) Medical Centre Leeuwarden, Department of Cardiology, Leeuwarden

Background Left ventricular heart failure is a well-known risk factor for outcome in cardiac surgery. However, data on the clinical relevance of right ventricular (RV) failure are limited. Aim To establish the prognostic implications of RV failure in a large series of post cardiac surgery patients. Methods We performed a single-centre retrospective analysis of 1109 high-risk cardiac surgery patients in a four year period. By protocol patients were equipped with a pulmonary artery catheter, enabling continuous RV ejection fraction (RVEF) measurements. RVEF was categorized into three subgroups: RVEF < 20%, 20-30% and >30%. Primary outcome was two year all-cause mortality.

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Results Median follow-up time was 739 days. All-cause two year mortality was significantly different across groups: 4.1% for patients with RVEF >30%, 8.2% in the group with RVEF 20-30%, and 16.7% for patients with RVEF <20%, p<0.001. In a multivariate analysis, RVEF as a continuous variable was independently associated with the primary outcome (odds ratio 0.946 confidence interval 0.906-0.987, P=0.011.) Odds ratios for RVEF<20% were 1.878 (confidence interval 1.176-3.001, p=0.008) Conclusions RV function is independently associated with two year all-cause mortality in a heterogenic high-risk cardiac surgery population.

Abstract 8 - selected for short Power talk Disease and treatment characteristics in patients with newly diagnosed Polycytemia Vera: A Detailed Population-Based Study. T. Wustman (1), R.E. Kibbelaar (2), E.N. Van Roon (1), D. Sanel (1), S. Hovenga (3), G.J. Veldhuis (4), B. Van Rees (5), E.G. De Waal (1), R.S. Van Rijn (1), H. De Wit (6), N. Veeger (1), M. Hoogendoorn (1). (1) Medical Center Leeuwarden, Leeuwarden (2) Department of Pathology, Pathology Friesland, Leeuwarden (3) Department of Hematology, Nij Smellinghe, Drachten (4) Department of Hematology, Antonius Hospital, Sneek (5) Department of Hematology, Tjongerschans, Heerenveen (6) Department of Clinical Chemistry, Certe, Leeuwarden

Background Polycythemia Vera (PV) is a chronic clonal myeloproliferative neoplasm (MPN) associated with substantial symptom burden, symptomatic splenomegaly and a heightened risk of lifethreatening complications such as thromboembolic events or progression to acute myeloid leukemia (AML) or secondary myelofibrosis (MF) . Randomized controlled trials provide enriched information on PV but clinical data from these studies may not directly be translated to daily clinical practice due to strict inclusion criteria, excluding the more elderly patients or those with significant comorbidity. Aim We performed a detailed descriptive population-based cohort study in patients with newly diagnosed PV over a period of 10 years to determine PV-related symptom burden, including preceding thrombotic events, the occurrence of thrombosis and transformation to AML and/or MF under therapy in a real-world setting.

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Methods All patients with newly diagnosed PV in Friesland during the period of 2004 till January 2014 with a follow-up until December 2014 were retrieved from HemoBase. Patient demographics, preceding arterial and venous thrombosis, PV-related symptoms, palpable splenomegaly, laboratory data and treatment characteristics were obtained. Occurrence of thrombosis, transformation to MF or AML and causes of death were registered. Results 112 patients with newly diagnosed PV ( median age 68 years (range 32 to 91 years) in Friesland were observed, resulting in an incidence of 1.7 per 100.000 per year. A total of 45 patients (40%) had a history of thrombosis. At presentation 25% of patients had PV-related symptoms and 13% a palpable splenomegaly. Phlebotomy was initiated in 56%, the majority of patients (66%) received hydroxyureum (HU) as first-line treatment, and 83% were ultimately exposed to treatment with HU. Intolerance for HU was observed in 14% of patients. After a median follow-up (FU) of 33 months (range, 0-125 months) 19 patients (17%) died in whom 3 patients (16%) the death was regarded PV-related. Gender, comorbidities, intolerance to HU and thromboembolic complications before diagnosis and during FU were not significantly associated with overall survival. Nine thrombosis (8%) occurred in 8 patients at a median follow-up of 8.5. months (range 2.5. – 23 months). Only two patients with transformation to AML and MF (1.7%) were observed after a follow-up time of 58 and 78 months, respectively. Conclusions This unique detailed population-based cohort study in newly diagnosed PV patients showed that symptomic burden of PV at diagnosis is substantial and a large proportion of patients have a preceding thrombosis. During FU thrombosis were predominantly observed in the first year of treatment and progression to AML or MF was relatively rare.

Abstract 9 - selected for short Power talk A Comparison Between the Metronome-Paced Tachypnea Test and Cardiopulmonary Exercise Testing in Detecting Dynamic Hyperinflation in an Average COPD Population. E. Vis (1), A. Hoekstra - Kuik (1), N.J.G.M. Veeger (2), A. ten Brinke (1), J.V.D. Maten (1). (1) Department of pulmonology (2) Department of Clinical Epidemiology, Medical Centre Leeuwarden, Leeuwarden, Netherlands

Background Dynamic hyperinflation (DH) resulting from expiratory flow limitation is seen in patients with moderate to severe COPD (O’Donnell, 2001). DH can be detected using cardiopulmonary exercise testing (CPET). The metronome-paced tachypnea test (MPT) has shown to be an alternative test in detecting DH in a cohort of rehabilitation patients with COPD (Lahaije, 2013).

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Aim To investigate whether the MPT is a useful test in detecting DH in comparison to CPET in an average COPD population in daily practice. In addition, we analyzed whether DH was associated with clinical baseline characteristics. Methods In this observational study we included 63 patients with COPD (GOLD I-IV), age 43-83 years, referred for CPET because of rehabilitation (n=35), dyspnea analysis (n=20) and VO2max (n=8). Baseline characteristics included MRC and CCQ questionnaire, exacerbation rate and hospitalization in the preceding year. The patients performed CPET and MPT on the same day. Patients with a decline in inspiratory capacity (∆IC) of >10% were classified as having DH (Lahaije, 2013). Results Baseline characteristics showed patients with COPD GOLD I (n=6), GOLD II (n=32), GOLD III (n=17) and GOLD IV (n=8). Patients with DH in COPD GOLD II-III showed a larger ∆IC for both MPT and CPET. In comparison to CPET we found a sensitivity of 84% and specificity of 63% for detecting DH with MPT. MPT showed a larger ∆IC than CPET (mean ± SD: 0.6 ± 0.4 vs 0.51 ± 0.4 L; p=0.01). For MPT DH group showed a trend of higher MRC score versus non DH group (2.7 ± 1.3 vs. 2.3 ± 1.2; p=0.051) and more exacerbations in the preceding year (1.02 ± 1.35 vs. 0.13 ± 0.35; p=0.051). Patients with DH used more long-acting bronchodilators (p<0.01). No difference in CCQ was found (2.34 ± 1.2 vs. 1.95 ± 1.0; p=0.63). For CPET no such differences were found except for use of LAMA (p=0.016). Conclusions In a general population with COPD GOLD I-IV referred for CPET for various reasons the MPT test is adequate to detect DH when compared to CPET. Additionally we found a suggestion for higher disease burden in DH group identified with MPT. This was not seen in CPET. This implicates that a cluster of COPD patients with higher disease burden can be identified with MPT. To explore this, more investigation is warranted in a larger population.

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Abstract 10 - selected for short Power talk Clinical, ultrasound and radiographic evaluation of hip joints in ankylosing spondylitis patients with active disease. F.R. Wink (1,2), F. Maas (2), G.A.W. Bruyn (3), E. van der Veer (4), H. Bootsma (2), E. Brouwer (2), S. Arends (1,2), A. Spoorenberg (2). (1) Rheumatology, Medical Center Leeuwarden, Leeuwarden (2) Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen (3) Rheumatology, MC Groep Hospitals, Lelystad (4) Laboratory Medicine, University Medical Center Groningen, Groningen

Background Hip involvement is a characteristic extra-spinal manifestation of ankylosing spondylitis (AS). Inflammation of the hip joints may lead to structural damage. Hip involvement in AS is associated with more severe disease and functional impairment. Aim To assess the prevalence of hip involvement in AS patients with active disease and to investigate the mutual associations between the different assessments used to evaluate hip involvement. Methods Between 2004 and 2008, consecutive outpatients from the GLAS cohort before starting TNF-alpha blocking therapy with radiographs of the pelvis and available Power Doppler US examination of the hip joints were included. All patients fulfilled the modified New York criteria for AS. History of hip involvement was assessed and the following assessments were evaluated in both hip joints seperately: tender hip joint, PDUS examination for both inflammatory and structural lesions and the BASRI-hip (0-4) to assess structural radiographic hip involvement. This was defined as BASRIhip score >=2. To investigate the mutual associations between these different assessments of hip involvement Chi-square, Phi coefficients and percentage concordance were calculated. Results Mean age of the 111 included patients was 43 years, median symptom duration was 15 years, 71% was male and 81% was HLA-B27 +. History of hip involvement was present in 22 (20%) patients. 25 (23%) patients had >=1 tender hip joint. PDUS examination showed inflammatory lesions in 19 (17%) and structural lesions in 22 (20%) patiens. Structural radiographic damage of at least one hip joint was seen in 11 (10%) patients. A strong correlation was found between history of hip involvement and BASRI-hip total score >= 2. Moderate correlations were found between BASRIhip score >= 2 and structural PDUS lesions and between structural PDUS lesions and tender hip joints. As to the other assessments of hip involvement no significant correlations were found. The concordance rates were relatively high due to overall few hip abnormalities.

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Conclusions In this cohort study the prevalence of hip involvement in AS patients with active disease ranged between 10% and 23% depending on which assessment used. The strongest correlation was found between radiographic hip joint damage and the history of hip involvement. Surprisingly, no association was found between tender hip joints assessed with physical examination and the inflammatory PDUS lesions.

Abstract 11 - selected for short Power talk Strooistraling afkomstig van de Mini C-boog tijdens hand-/pols operaties. Juliaan van Rappard (1), Tijmen de Jong (1), Willy Hummel (2), Chantal Mouës (1). (1) Afdeling Plastische Chirurgie, Medisch Centrum Leeuwarden (2) Klinisch Fysicus, Medisch Centrum Leeuwarden

Inleiding Tijdens het gebruik van de mini C-boog voor doorlichting peroperatief worden zowel patiënt als OK-personeel blootgesteld aan potentieel schadelijke röntgen-strooistraling. Het is bekend dat blootstelling hieraan een verhoogde kans geeft op het ontwikkelen van maligniteiten, huid afwijkingen, haematologische veranderingen en glaucoom. De stralingsbelasting voor nietblootgestelde werknemers is gemaximaliseerd op 1 mSv/jr voor het lichaam en 50 mSv/jr voor de handen. Het doel van deze studie is de hoeveelheid strooistraling te kwantificeren waaraan de chirurg en zijn assistent worden blootgesteld tijdens het gebruik van de mini C-boog gedurende standaard hand-pols ingrepen, met inachtneming van de stralingshygiëne. Methode Gedurende een periode van vijf maanden is tijdens iedere chirurgische hand-/pols ingreep waarbij de mini C-boog moest worden gebruikt, de strooistraling gemeten. Loodschorten en schildklierbeschermers voor de eerste en tweede operateur werden vooraf geprepareerd met een dosimeterset bestaande uit een conventionele dosimeter (NRG) en een Realtime dosimeter (Raysafe). Ook werd door beide operateurs een ringdosimeter om de niet-dominante index vinger gedragen. Veilig gebruik van de mini C-boog werd bereikt door gebruik te maken van de laser pointer, de doorlichttijd tot een minimum te beperken en de handen van de chirurg buiten de primaire bundel te houden. Resultaat Tijdens de studieperiode is de mini C-boog gebruikt bij 93 chirurgische ingrepen; 36 vinger-, 26 hand- en 31 pols operaties, waarbij totaal 1873 seconden is doorlicht. Alle vier de conventionele dosimeters laten ieder een cumulatieve dosis zien van <0.01 mSv (onder de detectiegrens). De Realtime dosimeters hebben een cumulatieve dosis van 28.94 µSv en 11.48 µSv gemeten ter hoogte van het epigastrio (respectievelijk hoofdoperateur, mede operateur) en 12.15 µSv en 11.32 µSv voor de schildklier positie. De cumulatieve ringabsorptie voor beide ringdosimeters bedraagt 1.28 mSv en 0.20 mSv.

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Conclusie De resultaten laten zien dat bij veilig gebruik van de mini C-boog tijdens chirurgische hand-/pols ingrepen de strooistraling dosis acceptabel is voor het lichaam en de handen van de chirurg. Over een periode van 5. maanden werd voor het lichaam 2.56% en voor de handen 2.8% van de jaarlijks toegestane stralingsdosis bereikt. Op basis van het ALARA-principe (As Low As Reasonably Achievabel) wordt geadviseerd loodbescherming te dragen en als operateur nog waakzamer te zijn met betrekking tot straling van de eigen handen. Daarnaast moet veilig gebruik van de mini C-boog zoveel mogelijk worden nagestreefd.

Abstract 12 - selected for short Power talk Vriescoupe-gecontroleerde excisie van huidmaligniteiten in het gelaat; analyse van de betrouwbaarheid en het klinische beloop. Kor H. Hutting (1), Drs. Paul G. Bos (1), Drs. Pauline M. Huizinga (1), Drs. Niels A. Noordzij, Dr. Chantal M. Mouës-Vink (1). (1) afdeling Plastische chirurgie en handchirurgie, Medisch Centrum Leeuwarden, Leeuwarden

Achtergrond Niet-melanocytaire huidmaligniteiten (NMSC) in het gelaat, bestaand uit basaalcelcarcinomen (BCC) en plaveiselcelcarcinomen (PCC), worden in het MCL behandeld met vriescoupegecontroleerde excisie (VCE) als reconstructieve sluiting preoperatief noodzakelijk lijkt. De peroperatieve radicaliteitsbepaling op vriescoupes wordt postoperatief gecontroleerd met paraffinecoupe-onderzoek. Doel Vaststellen van de betrouwbaarheid van radicaliteitsbepaling met vriescoupe-onderzoek bij de excisie van NMSC en bepalen van de effectiviteit van VCE als behandeling van NMSC in het gelaat. Methode Van 910 behandeltrajecten werden de uitkomsten van het vriescoupe-onderzoek retrospectief vergeleken met de uitkomsten van paraffinecoupe-controles, de gouden standaard voor histologische controle. Het percentage overeenkomstige uitslagen en de sensitiviteit en specificiteit van het vriescoupe-onderzoek werden bepaald. De effectiviteit van VCE als behandeling werd uitgedrukt als het percentage en als incidentie van recidieven. Hiervoor werd retrospectief onderzoek in het Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief (PALGA) verricht. Resultaten De uitkomst van het vriescoupe-onderzoek werd in 98,5.% (95%-betrouwbaarheidsinterval (BI): 97,5.-99,3%) van de gevallen bevestigd door de paraffinecoupe-controle. De sensitiviteit was 68,8% (95%-BI: 41,3-89,0%) en de specificiteit was 99,9% (95%-BI: 99,3-100,0%). De sensitiviteit en

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specificiteit verschilden niet significant tussen BCC’s en PCC’s. Bij 504 NMSC’s met een follow-up duur van minstens 3 maanden (gemiddeld 24,4 maanden) ontstonden 22 recidieven (4,37%, 95%-BI: 2,83-6,43%). De incidentie van recidieven bedroeg 2,18 (95%-BI: 1,40–3,25) per 100 persoonsjaren. Deze verschilde significant (p = 0,038) tussen BCC’s met 1,79 (95%-BI: 1,06-2,84) per 100 persoonsjaren, en PCC’s met 5.,31 per 100 persoonsjaren (95%-BI: 2,15-11,04). Conclusie Radicaliteitsbepaling met vriescoupe-onderzoek bij de excisie van NMSC is betrouwbaar door een hoog percentage overeenkomsten met de paraffinecoupe-controle en een acceptabele sensitiviteit en specificiteit. Wanneer radicale excisie met vriescoupe-onderzoek is bewezen kan direct tot reconstructieve sluiting worden overgegaan. Behandeling van NMSC met VCE is bewezen effectief door een laag percentage en een lage incidentie van recidieven. Het percentage recidieven is hoger bij PCC’s, maar valt binnen de beschreven resultaten van Mohs’ chirurgie (0-5.,9%).

Abstract 13 - selected for short Power talk Conventional CABG or On Pump Beating Heart: a difference in myocardial injury? Kornelis J. Koopmans (1), Cornelis Visser (1), Fabiano Porta (2), Jan H.R. Eikelaar (2). (1) Department of Extracorporeal Circulation, Medical Center Leeuwarden, Leeuwarden, the Netherlands (2) Department of Cardiothoracic Surgery, Medical Center Leeuwarden, Leeuwarden, the Netherlands

Background Conventional extra corporeal circulation, with aortic cross-clamping and cardioplegic arrest, is the most frequently used technique of assistance for Coronary Artery Bypass Grafting (CABG). Alternatively CABG can be carried out without ECC (Off Pump Coronary Bypass Graffting; OPCAB) or with the use of a minimized ECC-system. CABG assisted by any form of ECC can be carried out either with or without cross-clamping of the aorta. Aim In our hospital two different techniques of extra corporeal circulation are used for Coronary Artery Bypass Grafting (CABG): conventional CABG (CCABG) and, if indicated, On Pump Beating Heart (OPBH). Indications for OPBH are impaired left ventricular function and/or a calcified ascending aorta. Our hypothesis was that OPBH, while aortic cross-clamping is avoided, would result in a lower degree of cardiac ischemia, compared to CCABG. To examine this we studied the differences in myocardial injury between patients with an ejection fraction > 30%

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Methods Forty patients were randomized to undergo either CCABG with aortic cross-clamping and crystalloid cardioplegic arrest (n = 20) or OPBH using a minimized system (n = 20). Troponin T, creatine kinase (CK) and creatine kinase-myocardial band (CK-MB) were measured preoperative, 10 minutes after administration of protamin, arrival Intensive Care Unit (ICU), 4 hours after arrival ICU and 10 hours after arrival at ICU. Results Our results show a less myocardial injury in patients undergoing the OPBH-technique. Troponin T was lower in the OPBH-group, showing significance at 4 hours after arrival at ICU (p = 0.028). CK was significantly lower in the OPBH-group at 10 minutes after administration of protamine (p = 0.000), arrival ICU (p = 0.000) and 4 hours after arrival ICU (p = 0.033). CK-MB in the OPBH-group was significantly lower at arrival at the ICU (p = 0.038). Conclusions In patients with an ejection fraction >30% who underwent the OPBH-technique there appeared to be a trend of lower myocardial injury than in patients with an ejection fraction > 30% who underwent CCABG. In this study, including patients with left ventricular ejection fraction above 30% undergoing elective coronary bypass grafting, the use of an on pump beating heart technique favored myocardial preservation, when compared to conventional extra corporeal circulation with cardioplegic arrest.

Abstract 14 - selected for short Power talk When to activate a multidisciplinary team for an acute abdominal aortic aneurism? M. Maltha (1), A. Visser (1), T. Sandjer (2), K. Jahrome (3), T.W.F. Vink (4), E. ter Avest (1). (1) Department of Emergency Medicine, Medical Centre Leeuwarden, the Netherlands (2) Medical manager EMS service RAV Fryslan (3) Department of Vascular Surgery, Medical Centre Leeuwarden, the Netherlands (4) Department of Radiology, Medical Centre Leeuwarden, the Netherlands

Background Despite advances in treatment over the past years with the introduction of endovascular aneurism repair (EVAR), the mortality of a ruptured AAA is high. Timely activation of a multidisciplinary aneurysm team can expedite both the diagnostic process and the shared decision-making and thereby contribute to a better outcome. However, it is often difficult to determine when such a team should be summoned based on the (often limited) pre-hospital information provided

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Methods We performed a retrospective cohort study of patients brought to our hospital between January 1st 2013 and October 1st 2014 by the emergency medical services (EMS) with a clinical suspicion of an acute AAA in order to identify patient characteristics that could be used for the development of evidence based activation criteria for multidisciplinary acute aneurysm teams. Results Of the 63 patients presented by the EMS with a clinical suspicion of an acute AAA, 16 had an acute AAA. “Age >70” (LR+ 2.6 [1.8-3.8], “SBP <137mm Hg” (LR+ 2.6 [1.5.-4.9], , “presence of diaphoresis“ (LR+ 2.5. [1.7-3.8] and a “prior history of AAA” (LR+ 2.9 [1.5.-5..7] were independent predictors of the presence of an acute AAA. The presence of any of these factors increased the pre-test probability of an acute AAA to > 50%. Conclusions Pre-hospital information regarding the patient’s age, history (known AAA), blood pressure and general appearance (presence of diaphoresis) should be obtained when EMS services announce the arrival of a patient with suspected acute AAA in order to determine if a multidisciplinary aneurism team should be activated early.

Abstract 15 – abstract only Nationwide review of mixed and non-mixed femoral and acetabular components from different manufacturers in total hip arthroplasty: a Dutch Arthroplasty Register study. Drs. R.M. Peters (1), Dr. ir. L.N. van Steenbergen (2), Prof. Dr. S.K. Bulstra (3), Dr. A.V. Zeegers (4), Dr. R.E. Stewart (5), Dr. R.W. Poolman (6), Dr. A.H. Hosman (3), Dr. W.P. Zijlstra (1), Dr. P.C. Rijk (1). (1) Department of orthopaedic surgery, Medical Center Leeuwarden, Leeuwarden (2) Landelijke Registratie Orthopedische Implantaten, s Hertogenbosch, The Netherlands (3) Department of orthopaedic surgery, University Medical Centre Groningen, Groningen, The Netherlands (4) Department of orthopaedic surgery, Medical Spectrum Twente, Enschede, The Netherlands (5) Department of epidemiology, University Medical Centre Groningen, Groningen, The Netherlands (6) Department of orthopaedic surgery, Onze Lieve Vrouwe Gasthuis, Enschede, The Netherlands

Background The usage of components from different manufacturers in implantation of mixed total hip arthroplasty (THA) is common in orthopaedic practices worldwide. Guidelines caution not to mix components. Therefore, there has been controversy between guidelines and practices of mixing implant components.

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Aim The aim of this study is to report on the use of mixed components in THA in the Netherlands. Furthermore, to determine the early results of mixed total hip arthroplasties and compare this with non-mixed THAs. Patients and Methods The Dutch Arthroplasty Register (LROI) is a nationwide population-based register that includes information about joint arthroplasties in the Netherlands since 2007. We retrieved descriptive data and arthroplasty characteristics, including name, type, material, head size and manufacturer of the prosthesis, from the LROI. Based on the manufacturer of the femoral stem, femoral head, and acetabulum component, four groups were categorized; the non-mixed group consisted THAs with components of the same manufacturer; a mixed group of THAs with a different manufacturer for the femoral stem and head component; a mixed group with difference in head and cup manufacturer and a mixed group with difference in the femoral stem, head and cup manufacturer. Mixed-prostheses are defined as THAs (stem, head and cup) composed out of components fabricated by different manufactures. We excluded all THAs with components of unknown or missing manufacturers. Results We analyzed 163,159 THAs in 2007-2014 in the Netherlands. Eleven percent of THAs were composed of mixed components (n=18,396). There was no significant difference between revision rates of mixed and non-mixed THAs. Revision of primary THAs due to loosening of the acetabulum as well as peri-articular ossification seemed to be more common in mixed THAs, while revision due to symptomatic metal-on-metal bearing seemed to be less common in mixed THAs. Conclusions In conclusion, based on the early Results of this nationwide analysis, the use of mixed THAs yields similar revision rates compared to non-mixed THAs, although long-term Results are unknown. Further studies on the use of mixed components in assembling THAs should be with a similar large cohort with long term follow up data on patient survival and the amount of revision procedures.

Abstract 16 – abstract only Effects of ketanserin on microcirculatory alterations in septic shock: an open label pilot study. Namkje A.R. Vellinga (1,2), Gerke Veenstra (1), Claudia Scorcella (1), Matty Koopmans (1), Eric N. van Roon (3), Can Ince (2), E. Christiaan Boerma (1,2). (1) Department of Intensive Care, Medical Center Leeuwarden, Leeuwarden (2) Department of Translational Physiology, Academic Medical Center Amsterdam (3) Department of Clinical Pharmacy and Pharmacology, Medical Center Leeuwarden

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Introduction Microcirculatory alterations in sepsis are associated with increased morbidity and mortality. These alterations occur despite macrohemodynamic resuscitation. Alternative promicrocirculatory strategies, including vasodilatory drugs have been suggested to improve capillary blood flow. Ketanserin, a serotonin receptor antagonist , is an attractive candidate, because of its vasodilatory, antithrombotic and anti-inflammatory effects. Methods This is an open label pilot study on the effect ketanserin administration on microcirculatory alterations in septic shock, defined as microvascular flow index (MFI) ≤ 2.5. after a strict macrohemodynamic resuscitation protocol. Sidestream Dark Field imaging (SDF) was applied to assess the microcirculation. A stepwise incremental dose regiment was applied until an MFI>2.9, the primary endpoint, was reached. Results Ten patients (APACHE IV 115 [100-136]) were included. Baseline MFI was 1.71 [1.31-2.32], significantly increasing to 2.96 [2.54-3.00] (P=0.021) during the ketanserin infusion. The total ketanserin dose was 0.09 [0.08-0.13] mg/kg per patient in 60 [30-60] minutes. In 3 patients (30%) the ketanserin infusion was discontinued due to refractory hypotension. Conclusions An improvement in microcirculatory perfusion was observed during ketanserin administration in patients with septic shock after macrohemodynamic resuscitation. This finding needs further exploration in a placebo-controlled setting. Trial registration: NCT01329887

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Abstract 17 – abstract only Monitoring of somatic parameters at outpatient departments for mood and anxiety disorders. M. Simoons (1,2,3), H. Mulder (1), B. Doornbos (4), R.A. Schoevers (2), E.N. van Roon (3,5), H.G. Ruhé (2). (1) Department of Clinical Pharmacy, Wilhelmina Hospital Assen (2) Department of Psychiatry, University of Groningen/University Medical Center Groningen (3) Unit of Pharmacotherapy and Pharmaceutical Care, Department of Pharmacy, University of Groningen (4) Mental Health Services Drenthe, Assen (5) Department of Clinical Pharmacy and Clinical Pharmacology, Medical Center Leeuwarden

Background The risk of early mortality from severe mental illness (SMI), including bipolar and major depressive disorder, is two or three times higher than in the general population. About 60% of this excess mortality is explained by somatic co-morbidities, which are induced or worsened by unhealthy lifestyle, disparities in health care access and adverse effects of psychotropic drugs. The need for somatic monitoring of patients with SMI is increasingly recognized and translated into monitoring guidelines. Suboptimal somatic monitoring may cause physical health problems possibly affecting the mental illness and treatment thereof to be unrecognized or misinterpreted. Aim To assess monitoring practices in outpatients with mood and anxiety disorders. Methods A retrospective review of patient records was performed to assess somatic monitoring in patients aged 18 years and older from four outpatient departments for mood and anxiety disorders in the northern part of The Netherlands. Primary outcome was the percentage of patients without monitoring measurements in their medical records. Secondary outcomes were monitoring frequency per parameter and average time from start of treatment to first measurement. We assessed monitoring frequencies of metabolic parameters in participants using a typical antipsychotics separately and also those of lithium serum concentration, thyroid and kidney function in patients using lithium. Results Of 324 patients, 186 (57.4%) had no monitoring measurements in their medical records during on average 7.8±9.3 months of treatment. For 66.4% of all patients and 45.3% of patients using atypical antipsychotics, no record of any metabolic measurement was available. Less than two tests of lithium serum concentration, thyroid and kidney function per year (minimum in Dutch Bipolar Disorder guideline) were performed in 17.9, 41.1 and 28.6% of patients using lithium. Moreover, the average time from start of treatment to first measurement was 6.9±4.6 months.

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Conclusions This study shows that somatic monitoring frequencies at outpatient departments for mood and anxiety disorders are low. For almost two-thirds of patients, no records of monitoring measurements were available. Moreover, almost seven months before a first monitoring measurement is performed indicate that a baseline screening is not routine practice in these outpatients. These monitoring practices need to be improved to prevent undetected somatic complications in SMI outpatients.

Abstract 18 – abstract only Medication discrepancies in outpatients with mood and anxiety disorders. Risks and clinical relevance. M. Simoons (1,2,3), H. Mulder (1), A.J. Risselada (1), F.W. Wilmink (4), R.A. Schoevers (2), H.G. Ruhé (2), E.N. van Roon (3,5). (1) Department of Clinical Pharmacy, Wilhelmina Hospital Assen (2) Department of Psychiatry, University of Groningen/University Medical Center Groningen (3) Unit of Pharmacotherapy and Pharmaceutical Care, Department of Pharmacy, University of Groningen (4) Department of Psychiatry, Wilhelmina Hospital Assen (5) Department of Clinical Pharmacy and Clinical Pharmacology, Medical Center Leeuwarden

Background Psychiatric patients may be more at risk for side effects as well as drug interactions than the general population because of their frequent co-use of psychiatric and somatic medications. A complete and accurate medication overview, as obtained by medication reconciliation with the patient, is essential to evaluate the clinical status and to allow correct adjustment of any pharmacotherapeutic treatment. An incomplete or erroneous medication overview may lead to prescribing errors and iatrogenic harm. Little is known about medication reconciliation quality at psychiatric outpatient clinics. Aim To identify discrepancies between the medication overviews of outpatient clinics for mood and anxiety disorders and the reconciled drug usage by their patients as well as to investigate the clinical relevance of those discrepancies. Methods A cross-sectional study was conducted at four outpatient departments for mood and anxiety disorders in the Northern part of the Netherlands. We assessed the discrepancies between the medication lists from the electronic medical records from the outpatient department and the actual medication use by outpatients of 18 years and older on the day of inclusion. The actual medication usage was determined by medication reconciliation with the patient. Primary outcome was the number of discrepancies on the inclusion date. Secondary outcome was the clinical

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relevance of the discrepancies, as assessed by an expert panel consisting of a psychiatrist and a hospital pharmacist/clinical pharmacologist, who independently reviewed each discrepancy for its potential to cause patient discomfort or clinical deterioration. Results At least one discrepancy in the medication overview was found in 348 of 367 patients (94.8%). The medication overview contained on average 3.9±2.8 discrepancies per patient. Most discrepancies were omitted drugs that were regularly used by the patient. 22.7% of all discrepancies, present in almost half of all patients (49.3%), had the potential to cause patient harm. Conclusions To our knowledge, this is the first study on medication discrepancies and their clinical relevance in psychiatric outpatients. We found on average 3.9 discrepancies in the medication overviews of the outpatient departments for mood and anxiety disorders. Furthermore, a substantial part of these discrepancies were considered to be a clinically relevant risk to medication safety in outpatients with mood and anxiety disorders.

Abstract 19 – abstract only Contribution of 18F-FDG PET/CT in patients suspected for colorectal cancer recurrence, with normal or increased CEA. H. Balink (1), E. van der Zee (1), J.P.E.N. Pierie (2), R.J. Bennink (3), H.J. Verberne (3). (1) Department of Nuclear Medicine (2) Department of Minimal Invasive Surgery, Medical Center Leeuwarden (3) Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam

Objective Colorectal cancer (CRC) is an increasing health problem in developed countries. Patients with a history of primary CRC surgically treated with the intention of curation benefit from an optimal postoperative follow-up. The current Dutch guidelines recommend computed tomography (CT) as the imaging modality of choice, whether or not indicated by an elevated carcinoembryonic antigen (CEA) level. However, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT, seems to have a better diagnostic precision than CT in detecting CRC recurrence. The objective of this retrospective study was to evaluate the diagnostic precision of 18F-FDG PET/ CT in detecting CRC recurrence during follow-up, after the primary CRC was surgically treated with curative intention. Patients were included with either a normal CEA level (and with equivocal radiology findings), or elevated CEA levels.

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Methods In total 124 were included. All patients with suspected recurrence of CRC during follow-up were subjected to 18F-FDG PET/CT imaging. A total of 124 18F-FDG PET/CT scans were assessed and the 18F-FDG PET/CT outcome was subsequently verified based on the findings during the followup period after 18F-FDG PET/CT. Results In the overall population, with a proven CRC recurrence prevalence of 68,6% (n = 85), 18F-FDG PET/CT had an overall sensitivity, specificity, and accuracy of 94,1% , 82,1% and 90,3% respectively. As expected patients with a normal CEA level (n = 25) had a lower CRC recurrence prevalence compared to those with an elevated CEA level (n = 94) (48% vs. 72%, p = 0.021). 18F-FDG PET/CT in CEA normal patients had a sensitivity, specificity, and accuracy of 91.7%, 84.6% and 88%, and for those patients with an elevated CEA level these values were 94,1%, 80,8% and 90,4%, respectively. The rate of increase in CEA levels was significantly higher in the group with recurrence/malignancy compared to the group with no recurrence: 0.146 versus 0.038 µg/l/day (p=0.001). Five patients had rapidly increasing CEA-levels below the cut-off value of 5. µg/l and were accordingly excluded. However, recurrence was found in all 5.. Conclusions 18F-FDG PET/CT showed, irrespective of CEA levels, a high diagnostic accuracy in detecting or excluding CRC recurrence during postoperative follow-up. The rate of increase in CEA levels seems more relevant than the actual values. These retrospective data are preliminary; the role 18F-FDG PET/CT in patients suspected for CRC recurrence needs to be confirmed in prospective trials.

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Abstract 20 – abstract only Preoperative Hemoglobin Level: The Best Predictor Of Transfusion Of Packed Red Cells. W.J. de Boer (1), C. Visser (1) and Y.M. Ganushchak (2). (1) Department of Cardio-Thoracic Surgery, Medical Center Leeuwarden, Leeuwarden, The Netherlands (2) Department of Cardio-Thoracic Surgery, Maastricht University Medical Center, Maastricht, The Netherlands

Blood transfusions are associated with several risks. Immunological reactions resulting from a blood transfusion are most common. Furthermore, blood transfusions are still a possible source of disease transmission. Optimized blood management can result in a reduction of blood transfusions. Clear guidelines and awareness among all employees of the heart centre of the Medical Centre Leeuwarden (MCL) have resulted in a reduction in transfusion rate in recent years. Between 2008 and 2013, the overall transfusion rate of all cardiothoracic patients decreased from 54.5.% (285/523) to 33.7% (260/771) for all blood products during the entire hospital stay. Identification of the group of patients that still received a blood transfusion in recent years, could result in a further reduction. This study enrolled 4022 patients undergoing cardiothoracic surgery between 2008 and 2013. Patients were divided into three groups: “no blood transfusion”, “transfusion of packed red cells only”, and “other blood transfusions”. In total, 16 variables were tested for their association with the administration of homologous blood. The variables associated with blood transfusion were included in a stepwise multinomial logistic regression analysis, to find the variables with the strongest association. For the transfusion of packed red cells only and other blood products, the following predictors are found: gender, age, weight, type of surgery, reoperation, unstable angina pectoris, active endocarditis, recent myocardial infarction, Preoperative creatinine level, Preoperative hemoglobin level and platelet count. The best predictor for the transfusion of packed red cells is preoperative hemoglobin level (4.1 to 7.8 mmol/l). For other blood products, the strongest association was found with type of surgery (aortic surgery, ventricular septal rupture and intracardiac tumour). Selective, preoperative treatment to increase hemoglobin level might reduce transfusions of packed red cells. The use of EPO preoperatively could be a helpful strategy.

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Abstract 21– abstract only Early learning curve of residents for laparoscopic colorectal surgery. Robbert J.I. Bosker (1,2), Henk Groen (3), Christiaan Hoff (1), Eric R. Totte (1), Rutger J. Ploeg (4) and Jean-Pierre E.N. Pierie (1*). (1) Department of Surgery, Medical Center Leeuwarden, Leeuwarden, The Netherlands and the Leeuwarden Institute for Minimally Invasive Surgery (LIMIS) (2) Department of Surgery, Deventer Hospital, Deventer, The Netherlands (3) Department of Epidemiology, University Medical Center, Groningen, The Netherlands (4) Department of Surgery, University Medical Center Groningen. Groningen, The Netherlands

Objective To evaluate the learning curve of resident surgeons for the laparoscopic rectosigmoid resection procedure; establish a minimum of cases before a resident surgeon could be expected to obtain competency with the procedure. Methods All patients with either benign or malignant disease who underwent a laparoscopic rectosigmoid resection from 2003 through 2007 were evaluated. The procedure was completed by a single resident surgeon (total 14) proctored by an experienced surgeon. A cumulative sum control chart (CUSUM) analysis was used evaluate performance. A procedure was defined as a failure if there was a required conversion to an open surgical procedure; development of major intra-operative complications such as intraabdominal organ injury, bleeding, or anastomotic leakage; or if an inadequate number of lymph nodes (<12 nodes) were removed. Results A total of 169 laparoscopic rectosigmoid resections were performed by the14 resident surgeons in the period evaluated. A significant majority of the resident surgeons were able to consistently perform the procedure without failure after 10 cases and determined to be competent. One resident surgeon was not determined to be competent after 10 cases and the CUSUM score supported these findings. Conclusions We concluded that a learning curve of at least 10 cases is required for most resident surgeons to obtain competence with the laparoscopic rectosigmoid resection procedure. Evaluation with the CUSUM analysis can be used to measure and support the clinical evaluation of the resident surgeon’s competence with the procedure.

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Abstract 22 – abstract only Optimizing postoperative outcomes after gastric bypass surgery - the influence of dietary protein and its amino acid composition. M. van den Broek (1), L.J.M. de Heide (1), N.J.G.M. Veeger (2,3), A.M. van der Wal – Oost (4), A.P. van Beek (5). (1) Department of Internal Medicine, Medical Center Leeuwarden, The Netherlands (2) Department of Epidemiology, Medical Center Leeuwarden, The Netherlands (3) Department of Epidemiology, University Medical Center Groningen, The Netherlands (4) MCL Academy, Medical Center Leeuwarden, The Netherlands (5) Department of Endocrinology, University Medical Center Groningen, The Netherlands

Background Bariatric surgery has emerged as an effective method to reduce morbid obesity. Nutritional counseling is essential in order to achieve maximal treatment success and to avoid long term complications. Increased dietary protein intake could have a beneficial influence on various postoperative results. Aim and Methods We conducted a systematic literature search of studies examining the relationship between dietary protein intake or supplementation with amino acids and postoperative outcomes after gastric bypass surgery. Results Nineteen studies were included with varying study designs, interventions and outcomes. For most postoperative outcomes, studies did not provide solid evidence of any beneficial effect. Only an increased dietary protein intake was associated with improved weight loss after gastric bypass surgery, but the level of evidence is low (Grade C). Conclusions The study of the influence of protein and its amino acid composition represents an important developing domain of knowledge and needs further attention considering the high popularity of bariatric surgery. For future study purposes, we recommend a clear description of the exact quantity and composition of the proteins and amino acids in the diet or supplement.

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Abstract 23 – abstract only Validatieproces K(N)UZS-8: vragenlijst kwaliteit van leven en patiënttevredenheid kinderen van 0-8 jaar met schisis en/of rhinolalia aperta. N.C. Busschers, K.Piek, P. Huizinga, C.M. Mouës-Vink. (1) Afdeling Plastische Chirurgie, Medisch Centrum te Leeuwarden

Inleiding Tot dusver bestaat er geen Nederlandse gevalideerde vragenlijst voor het meten van kwaliteit van leven en patiënttevredenheid bij kinderen van 0-8 jaar met een uitwendig zichtbare of niet uitwendig zichtbare schisis en/of rhinolalia aperta die worden behandeld binnen een schisisteam. Het doel van dit onderzoek is het ontwikkelen en valideren van de K(N)UZS-8; een vragenlijst waarmee de invloed van schisis op het sociaal, psychisch en lichamelijk functioneren kan worden bepaald. Materiaal en methode Het betreft een validatiestudie uitgevoerd in het Medisch Centrum Leeuwarden. Ouder(s)/ verzorger(s) van kinderen in de leeftijd van 0-8 jaar met een uitwendig (niet)zichtbare schisis en/ of rhinolalia aperta werd gevraagd een enquête van 68 vragen in te vullen. Samenstelling van de vragenlijst is gebeurd met behulp van inzichten verkregen door interviews met experts, ouders en patiëntenvereniging. De volgende stappen zijn doorlopen: 1) dimensies identificeren (verwijderen vraag indien ≥50% beantwoord met “niet van toepassing”) 2) vaststellen van de sub-schalen (KMO >0.6), 3) bepalen betrouwbaarheid (Cronbach’s alfa >0.7) en 4) bepalen interne validiteit middels de test-retest procedure (Pearson >0.7). Resultaten 129 ouder(s)/verzorger(s) werden aangeschreven waarvan 80 vragenlijsten konden worden geanalyseerd. In totaal werden 13 vragen ≥50% beantwoord met ‘’niet van toepassing’’ en verwijderd. Door de validatieprocedure werden nog eens 12 vragen verwijderd waarna 43 vragen konden worden ingedeeld in vier subschalen: tevredenheid betreffende functioneren schisisteam, operaties, sociaal en psychisch functioneren en dagelijks functioneren. De factorstructuur voldeed met een KMO-waarde van >0.6 op iedere subschaal van ieder item. De interne validiteit omvatte een Cronbach’s α variërend van 0.699 tot 0.955. De test-retest correlatie volgens Pearson leverde waarden variërend tussen 0.737 tot 0.910 op. Conclusie Door middel van deze vragenlijst kon een goed beeld worden verkregen van de kwaliteit van leven en patiënttevredenheid in de beoogde patiëntengroep. Op basis van dit validatieproces is zeer aannemelijk gemaakt dat de K(N)UZS-8 vragenlijst valide is en in vervolgonderzoek mag dit worden aangenomen.

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Abstract 24 – abstract only Vitamin D status of patients with very mild Alzheimer’s disease compared to patients with subjective memory complaints. Gooitzen S.J. Eggink (a), Nic Veeger (b), P. Van Walderveen (a), Dieneke Z.B. van Asselt (a,c). (a) Department of Geriatric Medicine, Medical Center Leeuwarden, Leeuwarden, the Netherlands (b) Department of Epidemiology, Medical Center Leeuwarden, the Netherlands (c) Present address: Radboud Alzheimer Center, Department of Geriatric Medicine, Radboud University Hospital, Nijmegen, the Netherlands (d) Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands

Background Current consensus is that hypovitaminosis D contributes to cognitive decline and the development of dementia. Therefore reduced vitamin D status can be expected in patients with very mild Alzheimer Dementia (AD). Objective This study tests the hypothesis that a reduced vitamin D status can be shown in patients with very mild Alzheimer Dementia (AD). Methods Using a retrospective cross sectional study design, Vitamin D status of ambulatory patients with very mild AD (MMSE≥ 20) from a large regional memory clinic in The Netherlands was compared to patients with subjective memory complaints (SMC). Results 391 newly diagnosed mild AD-patients (median MMSE 24) and 96 SMC-patients (median MMSE 28) who visited our memory clinic between 2006 and 2014 were included. AD-patients were more often female (61% versus 49%), had lower body mass index (BMI: 26.0 versus 27.0) and were older (80 versus 76 years of age) than SMC-patients, respectively. Cardiovascular disease was more prevalent in SMC-patients as compared to AD-patients (47% versus 30% respectively). With 70%, vitamin D deficiency (<50 nmol/L) prevalence was high. No difference in vitamin D status between patients with very mild AD and SMC was found, both in crude results as well as after correction for relevant confounding factors. Conclusions In a large cohort of ambulatory patients with mild AD no evidence for an association between vitamin D and Alzheimer’s disease was found.

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Abstract 25 – abstract only The study design of CarniFit: a randomized controlled double-blind intervention study in frail elderly. Marjanne van der Hoek (1, 2, 3), Arie Nieuwenhuizen (2), Dieneke van Asselt (4), Feike van der Leij (3), Jaap Keijer (2). (1) MCL academie, Medical Center Leeuwarden, Leeuwarden (2) Human and Animal Physiology, Wageningen University, Wageningen (3) Food and Dairy Applied Research Centre, VHL University of Applied Sciences, Leeuwarden (4) Klinische geriatrie, Radboud University Medical Center, Nijmegen

Background Ageing is associated with increasing physical disabilities and prevalence of frailty, which negatively affects quality of life. In addition, ageing is also associated with a decrease in intramuscular carnitine levels. Simultaneously, intramuscular mitochondrial content and function decline. Therefore, it has been suggested that low intramuscular carnitine levels in the elderly may contribute to decreased mitochondrial function and this could subsequently lead to the geriatric symptom of frailty. We hypothesize that carnitine plays an essential role in health, especially in the pathogenesis of frailty in the elderly. Aim To study the effect of 24 weeks of carnitine supplementation on physical performance in frail elderly, ageing 75 years or older. In addition, we will investigate in a substudy the differences in carnitine status between healthy young individuals, fit elderly and frail elderly (n = 52). Methods The CarniFit study is a randomized, placebo controlled, double blind intervention study, in which 296 pre-frail/frail elderly (Fried score ≥ 1) ageing 75 years or older (n = 296) will be included. They will receive either 2 gram of L-carnitine supplements per day or placebo. At baseline, after 12 weeks and after 24 weeks, several measuremenst will be performed, including 400-meter walk gait speed as a measure for physical performance, blood carnitine levels, Short Physical Performance Battery, and the frailty score. In addition, we will investigate in a subgroup (n = 52) the effect of the carnitine intervention on the intramuscular carnitne levels. Moreover, we will investigate the differences in carnitine status and physical performance between healthy young inviduals (n = 26), fit elderly (n = 26) and frail elderly (n = 52). The CarniFit study will start in the first half of 2016.

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Abstract 26 – abstract only Hydrochloorthiazide heeft geen toegevoegde waarde bij de behandeling van op de intensive care ontstane hypernatriëmie. M.C.O. van IJzendoorn (1), H. Buter (1), W.P. Kingma (1), G.J. Navis (2), E.C. Boerma (1). (1) Intensive Care, Medisch Centrum Leeuwarden, Leeuwarden (2) Inwendige geneeskunde/nefrologie, Universitair Medisch Centrum Groningen, Groningen

Achtergrond Bij 6-9% (1) van de patiënten die op de intensive care (IC) van het MCL worden opgenomen onstaat hypernatriëmie (IAH). Dit wordt mogelijk mede veroorzaakt door een verminderde renale excretie van natrium. In eerdere literatuur wordt gesuggereerd dat IAH mogelijk te behandelen is met thiaziden door verhoging van de natriumexcretie (2,3). Doel Primair eindpunt: een daling van 3 mmol/l in sNa bij behandeling met hydrochloorthiazide (HCT) ten opzichte van placebo. Secundair eindpunt: verschil in urinenatrium (uNa). Methoden Middels een dubbelblinde placebogecontroleerde studie werden 50 patiënten op de IC met IAH, gedefinieerd als sNa ≥ 143 mmol/l, en een totale renale kationexcretie (natrium + kalium) lager dan sNa gerandomiseerd voor HCT 1dd 25mg of placebo gedurende maximaal 7 dagen. Gedurende de studie werd 24-uurs urine verzameld. Exclusiecriteria waren continue veno-veneuze hemofiltratie, gebruik van > 120mg furosemide/24 uur, centrale of nefrogene diabetes insipidus of gebruik van medicamenten die dit kunnen induceren, diurese < 400ml/dag en gebruik van HCT < 48 uur voor urinescreen. Resultaten Er was bij inclusie geen verschil in basale karakteristieken, serumnatrium, urinenatrium of vochtbalans tussen beide groepen. De mediane deelnameduur aan de studie in dagen was gelijk in beide groepen (HCT: 7 [4-7], placebo 6 [4-7], p = 0.64). Aan het einde van de studieperiode was de mediane afname van sNa in beide groepen 4 mmol/l (HCT: [1-9], placebo [2-6], p = 0.47). Ook de mediane toename in renale natriumexcretie was gelijk, namelijk 46 [26-86] mmol/l in de HCTgroep en 36 [9-78] mmol/l in de placebogroep (p = 0.31). Conclusie HCT heeft geen toegevoegde waarde bij de behandeling van IAH. Bij patiënten met IAH werd een daling van serumnatrium en een stijging van urinenatrium waargenomen gedurende de studieperiode, maar HCT ten leek dit niet te beïnvloeden.

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1. Koopmans M, Egbers P, Boerma E. The influence of a switch from NaCl based colloids to sodium acetate based colloids on the incidence of hypernatremia on the ICU. Intensive Care Med. 2010; 36:S140. 2. Overgaard-Steensen C, Ring T. Clinical review: Practical approach to hyponatraemia and hypernatraemia in critically ill patients. Crit Care. 2013;17(1):206. 3.Fliser D, Haller H. Modern differential therapy with diuretics. Internist (Berl). 2004;45(5.):598-605.

Abstract 27 – abstract only The Pareto-analysis for establishing content criteria in surgical training. Kelvin H. Kramp (1). Marc J. van Det (1,2) Nic J.G.M. Veeger (3,4) Jean-Pierre E.N. Pierie (1,5). (1) Department of Surgery, Leeuwarden Medical Centre, Leeuwarden, the Netherlands (2) Department of Surgery, Hospital Group Twente, Almelo, the Netherlands (3) Department of Epidemiology, Leeuwarden Medical Centre, Leeuwarden, the Netherlands (4) University of Groningen, University Medical Centre Groningen, Department of Epidemiology, Groningen, the Netherlands (5) Post Graduate School of Medicine, University

Background Currently, there is no widely used method to calibrate in vitro surgical training to the in vivo challenges during surgery on patients. The Pareto-principle states that in any population that contributes to a common effect a relative few account for the bulk of the effect. Aim This is the first study that evaluates the Pareto-principle for establishing content criteria for surgical training. Methods Verbal corrections of supervising surgeons during a laparoscopic cholecystectomy performed by trainees in the OR were documented and tallied. The corrections were rank-ordered and a cumulative distribution curve was used to calculate which corrections accounted for 80% of the total number of verbal corrections. Results The behaviour of 9 surgeons supervising 62 laparoscopic cholecystectomies performed by 12 novice trainees were analyzed. In total, 235 different verbal corrections were used 1570 times and were categorized into 40 different clusters of Aimed changes in novice behaviours. The 32 highest ranking verbal corrections (14%) and the 11 highest ranking clusters (28%) accounted for 80% of the total number of verbal corrections.

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Conclusions The Pareto-principle is a highly potential tool for identifying the few types of novice behaviour that account for the majority of corrections given by supervisors during a laparoscopic cholecystectomy on humans. Replicating this study for other surgical procedures could be an opportunity for creating surgical training tools that are more effectively calibrated to on-the-job challenges.

Abstract 28 – abstract only iLift: a health behavior change support system for lifting and transfer techniques to prevent lowerback injuries in healthcare. Derek A. Kuipers (a), Bard O. Wartena (a,e), Boudewijn H. Dijkstra (a), Gijs Terlouw (a), Job T.B. van t Veer (a), Hylke W. van Dijk (a), Jelle T. Prins (b), Jean Pierre E.N. Pierie (c,d). (a) NHL University of Applied Sciences, Leeuwarden, The Netherlands (b) MCL Academy of Leeuwarden, The Netherlands (c) Medical Center Leeuwarden, Surgery department, Leeuwarden, The Netherlands (d) Post Graduate School of Medicine, University Medical Center Groningen, University of Groningen, The Netherlands (e) University of Technology Delft, Industrial Design Engineering, The Netherlands

Background Lower back problems are a common cause of sick leave of employees in Dutch care homes and hospitals. In the Netherlands over 40% of reported sick leave is due to back problems, mainly caused by carrying out heavy work. Aim The goal of the iLift project was to develop a game for nursing personnel to train them in lifting and transfer techniques. The main focus was not on testing for the effectiveness of the game itself, but rather on the design of the game as an autogenous trigger and its place in a behavioral change support system. In this article, the design and development of such a health behavior change support system is addressed, describing cycles of design and evaluation. Methods (a) To define the problem space, use context and user context, focus group interviews were conducted with Occupational Therapists (n=4), Nurses (n=10) and Caregivers (n=12) and a thematic analysis was performed. We interviewed experts (n=5.) on the subject of lifting and transferring techniques. (b) A design science research approach resulted in a playable prototype. An expert panel conducted analysis of video-recorded playing activities. (c) Field experiment: We performed a dynamic analysis in order to investigate the feasibility of the prototype through biometric data from player sessions (n=620) by healthcare professionals (n=37).

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Results (a) Occupational Therapists, Nurses and Caregivers did not recognise a lack of knowledge with training in lifting and transferring techniques. All groups considered their workload, time pressure and a culturally determined habit to place the patient’s well being above their own as the main reason not to apply appropriate lifting and transferring techniques. This led to a shift in focus from a serious game teaching lifting and transferring techniques to a health behavior change support system containing a game with the intention to influence behavior. (b) Building and testing (subcomponents of ) the prototype resulted in design choices regarding players perspective, auditory and visual feedback, overall playability and perceived immersiveness. This design process also addressed the behavior shaping capacities of the game and its place within the health behavior change support system. An expert panel on lifting and transferring techniques validated the provoked in-game activities as being authentic. (c) Regression analysis showed an increase of the game score and dashboard score when more sessions were played, indicating an in-game training effect. A post-hoc test revealed that from an average of 10 playing sessions or more, the dashboard score and the game score align, which indicates behavioral change towards executing appropriate static lifting and transferring techniques. Conclusions Data gathered in the final field test shows an in-game training effect, causing players to exhibit correct techniques for static lifting and transferring techniques but also revealed the necessity for future social system development and especially regarding intervention acceptance. Social system factors showed a strong impact on the games persuasive capacities and its autogenous intent.

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Abstract 29 – abstract only Facet joint involvement and progression in the cervical spine of patients with ankylosing spondylitis treated with TNF inhibitors. Fiona Maas (1), Anneke Spoorenberg (1,2), Elisabeth Brouwer (1), Eveline van der Veer (3), Hendrika Bootsma (1), Rizwana Chaudhry (1), Monique Efde (2), Freke Wink (2), Suzanne Arends (1,2). (1) Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen (2) Rheumatology, Medical Center Leeuwarden (3) Laboratory Medicine, University Medical Center Groningen, University of Groningen, The Netherlands

Aim To investigate the prevalence and incidence of radiographic facet joint involvement in comparison to damage of vertebral bodies in the cervical spine of AS patients treated with TNF inhibitors. Second, to explore the association of facet joint involvement with patient characteristics and clinical outcome. Methods Consecutive patients from the Groningen Leeuwarden AS (GLAS) cohort who started treatment with TNF inhibitors because of active disease were included. Available lateral radiographs of the cervical spine at baseline and after 4 years of follow-up were scored by two trained and independent readers blinded to patient characteristics and time sequence. Facet joints of C2-C3 up to C6-C7 were scored according to the method of de Vlam et al. (0: normal, 1. joint space narrowing or erosion, 2. partial blurring or ankylosis, 3. complete blurring or ankylosis). Definite damage and progression of facet joints was defined as the presence and development of partial/complete blurring or ankylosis (score ≥2) in ≥1 facet joint, respectively. The modified Stoke AS Spine Score (mSASSS) was used to assess radiographic damage of the vertebral bodies. Definite damage and progression was defined as the presence and development of ≥1 (bridging) syndesmophyte, respectively. Results Of 99 included patients, 76% were male, mean age was 42±11 years, median symptom duration 16 years (range 1-47), 84% were HLA-B27 positive, mean BASDAI was 5..9±1.6, and mean ASDAS 3.8±0.8. At baseline, 25 (25%) had definite facet joint damage and 51 (52%) had definite damage of vertebral bodies at baseline. Damage of facet joints was exclusively seen in 5. (5.%) patients. Patients with facet joint damage had significantly longer symptom duration, more often a history of extra-articular manifestations, higher disease activity (ASDAS, CRP), larger occiput-to wall distance, and more damage of the vertebral bodies. After 4 years of follow-up, 13 (13%) patients

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showed definite progression of facet joints whereas 26 (26%) showed definite progression of vertebral bodies. Progression of facet joints without progression of vertebral bodies was seen in 8 (8%) patients. Conclusions Facet joints of the cervical spine are frequently involved in AS patients and slow radiographic progression was seen after 4 years of TNF blocking therapy. A small proportion of patients showed radiographic damage and progression at the facet joints without involvement of the vertebral body.

Abstract 30 – abstract only Gender differences in disease activity, physical function and quality of life in ankylosing spondylitis. Boukje van der Slik (1), Fiona Maas (1), Elisabeth Brouwer (1), Freke Wink (2), Monique Efde (2), Hendrika Bootsma (1), Suzanne Arends (1,2), Anneke Spoorenberg (1,2). (1) Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen (2) Rheumatology, Medical Center Leeuwarden, The Netherlands

Background The clinical presentation of ankylosing spondylitis (AS) differs between genders. Aim To investigate differences in clinical assessments of disease activity, physical function and quality of life between male and female patients with AS before starting TNF-α inhibitors and after 2 years of follow-up. Methods Patients from the Groningen Leeuwarden Axial SpA (GLAS) cohort who started TNF-α blocking therapy because of active disease were included based on the presence of a visit at baseline and after 2 years of follow-up. At these visits, disease activity was assessed using the BASDAI, ASDAS, CRP, patient GDA and physician GDA. Physical function and quality of life were assessed using the BASFI and ASQoL, respectively. Results For the 224 included AS patients with active disease, the mean age was 43±11 years, median duration of symptoms was 16 years (range 0-53), 68% were male and 80% were HLA-B27 positive. Patient characteristics were comparable between men and women. At baseline, female patients with AS experienced significantly higher disease activity according to BASDAI, ASDAS and patient GDA. Baseline CRP levels and physician GDA were comparable between genders. Furthermore, physical function (BASFI) and quality of life (ASQoL) were significantly worse in female patients.

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All clinical assessments improved significantly during 2 years of follow-up after starting TNF-α inhibitors. These improvements were comparable between male and female patients. Conclusions In this large cohort of AS patients in daily clinical practice, cross-sectional analysis showed that on self-reported assessments women experience higher disease activity and worse physical function and quality of life than men. Longitudinal analysis showed that the changes in clinical assessments during treatment with TNF-α inhibitors were comparable between male and female patients.

Abstract 31 – abstract only Slow spinal radiographic progression in patients with ankylosing spondylitis treated with TNF inhibitors. Fiona Maas (1), Suzanne Arends (1,2), Ivette Essers (3), Elisabeth Brouwer (1), Eveline van der Veer (4), Freke Wink (2), Monique Efde (2), Hendrika Bootsma (1), Anneke Spoorenberg (1,2). (1) Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen (2) Rheumatology, Medical Center Leeuwarden (3) Rheumatology, Maastricht University Medical Center (4) Laboratory Medicine, University Medical Center Groningen, University of Groningen, The Netherlands

Background Assessing radiographic progression in ankylosing spondylitis (AS) is challenging. A linear course of radiographic progression is seen in patients not treated with TNF inhibitors (TNFi), but results regarding the effect of this treatment are difficult to interpret due to methodological limitations. Aim To evaluate spinal radiographic progression over 2 to 8 years of follow-up in a large cohort of ankylosing spondylitis (AS) patients treated with TNFi. Methods Consecutive patients from the Groningen Leeuwarden AS (GLAS) cohort who started with TNFi because of active disease were included. Available radiographs at baseline and after 2 to 8 years of follow-up were scored in chronological time order by two trained and independent readers according to the modified Stoke AS Spine Score (mSASSS). Descriptive statistics for 0-2, 0-4, 0-6, 0-8 years and generalized estimating equations (GEE) in complete cases over 4 to 8 years were used to evaluate the course of spinal radiographic progression.

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Results In total, 188 patients were included; 70% were male, mean age was 42±11 years, median symptom duration was 14 years (range 1-53), 78% were HLA-B27 positive, and median baseline mSASSS was 2.5. (range 0-68). GEE analysis in complete cases revealed that radiographic progression follows an approximately linear course over 4 years (mean progression was 1.7 and 1.7 during 0-2 and 2-4 years) and follows a non-linear course over 6 years (mean progression was 1.8, 1.6, and 1.1 during 0-2, 2-4, and 4-6 years) and over 8 years (mean progression was 2.3, 1.4, 1.0, and 0.8 during 0-2, 2-4, 4-6, and 6-8 years). The deflection from a linear course over 6 and 8 years was also observed in the sensitivity analysis with data imputation of patients without complete data. Conclusions This observational study in AS patients treated with TNFi showed overall slow spinal radiographic progression with a deflection from a linear course during 6 to 8 years of follow-up.

Abstract 32 – abstract only Restoration of renal insufficiency in multiple myeloma is not associated with improved survival: a population based study. J. De Vries (1), B. Oortgiesen (2), M.H. Hemmelder (3), E. van Roon (2), R.E. Kibbelaar (4), N. Veeger (5), M. Hoogendoorn (1). (1) Department of Haematology, Medical Centre Leeuwarden, Leeuwarden (2) Department of Clinical Pharmacy & Pharmacology, Medical Center Leeuwarden, Leeuwarden (3) Department of Nephrology, Medical Centre Leeuwarden, Leeuwarden (4) Department of Pathology, Pathology Friesland, Leeuwarden (5) Department of Epidemiology, MCL Academy Leeuwarden, The Netherlands

Background renal insufficiency occurs in ±40% of the patients with multiple myeloma (MM) and is associated with a poor prognosis. Novel treatment strategies have shown great potential in restoring renal function. Current knowledge on the relationship between restoration of renal insufficiency and patient survival using a population-based approach is lacking. Aim To assess the effects of (partial) restoration of renal insufficiency on patient survival, efficacy of different (novel) treatment therapies and to identify parameters which may predict/affect patient survival on a population level in the Netherlands.

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Methods in a retrospective, population-based cohort study, a total of 131 patients with newly diagnosed MM between 01-01-2005 and 01-01-2014 with an eGFR<60ml/min at presentation were included in the study. Baseline characteristics, renal parameters and treatment details were obtained for each patient from Hemobase®, a database including all haematological malignancy patients in Friesland. Results a total of 80 (61%) patients achieved a renal response. Kaplan-Meier curves suggested a significantly improved survival in patients who achieved a renal response. However, when the analysis was corrected for the effect of early mortality (<2mth after diagnosis) and the time to response, the difference between the two groups disappeared (p=0.76). In the multivariate analysis, eGFR<30ml/min (p=0.01), age>70yrs (p=0.003), hypercalcaemia (p=0.001), and Lambda Bence-Jones (p=0.014) were independently associated with decreased survival. Conclusions achieving a renal response does not result in improved survival in patients who survive more than 2 months after diagnosis of MM.

Abstract 32 – abstract only Disease features and clinical course of Hairy cell leukemia, Hairy cell leukemia variant and splenic marginal zone lymphoma in a population-based registry. A.L. Noordhof, R.S. van Rijn. Medisch Centrum Leeuwarden.

Background Hairy cell leukemia (HCL), Hairy cell leukemia variant (HCL-v) and splenic marginal zone lymphoma (SMZL) are rare hematological diseases that can present with hairy cells. They have overlapping clinical and immunophenotypic features, so it can be difficult to make the right diagnosis. For the first time, the disease features of HCL, HCL-v and SMZL are inventoried together in a populationbased registry. Aim The aim was to determine if the disease features and clinical course indeed fitted the diagnosis that was once made in this population-based registry.

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Methods Using HemoBase®, an electronic health record used by all the hospitals in Friesland, a cohort between 2005 and 2015 was available. In this cohort, there were 25 HCL-patients, 14 HCL-v-patients and 18 SMZL-patients. Patient characteristics were inventoried (blood, bone marrow, imaging studies). Overall survival and disease free survival were determined. Results In this population, there was a relatively high number of HCL-v-patients. These patients made up 36% of HCL and HCL-v patients together. HCL-patients were younger than HCL-v- and SMZL-patients. Leukocytosis was only observed in HCL-v- and SMZL-patients. Leukocytopenia and thrombocytopenia were more frequent in HCLpatients. SMZL-patients more often showed an elevated LDH in comparison to HCL patients. The immunophenotypic profile of HCL, HCL-v and SMZL corresponds with the immunophenotypic profile as stated by the WHO classification. Additional markers were identified (CD10 and CD24) to possibly better differentiate between the three entities. Overall survival did not differ significantly. Median survival was not reached for any of the three entities. HCL-v-patients had relatively more lines of treatment. Disease free survival did differ (p = 0,005) between all three diseases, where HCL-v-patients had the shortest survival. Conclusions The characteristics of HCL, HCL-v and SMZL-patients in this population-based registry corresponds with the disease characteristics described in literature. After a first review, we could confirm the diagnosis once made. A remarkable finding is the high number of HCL-v-patients in this cohort, especially in the city of Leeuwarden. This suggests that there may be a (yet undiscovered) genetic or environmental factor in Friesland that has a role in the etiology of HCL-v. Future research should focus on further analysis of epidemiological and genetic factors of the HCL-v-patients. The possible finding of novel genetic driver mutations in HCL-v could give an unique insight in the pathophysiology of this rare disease.

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Abstract 34 – abstract only Non-focal transient neurological attacks are associated with cognitive impairment in patients with carotid occlusive disease. Laurien P. Onkenhout, (1*) Eline A. Oudeman, (1*) Catharina J.M. Klijn,(1,2) Ale Algra (1), L. Jaap Kappelle (1). * These authors contributed equally. (1) Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands (2) Department of Neurology, Donders Institute of Brain, Cognition and Behaviour, Center for Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands

Background Hemodynamic failure of the brain is associated with an increased risk of cognitive decline and probably also with an increased risk of transient neurological attacks (TNAs). We investigated whether a history of one or more non-focal TNAs was associated with decreased cognitive functioning in patients with carotid occlusive disease. Methods Fifty-three patients with internal carotid artery occlusion or high-grade stenosis, aged >50 years and no dementia, underwent standardized history taking and neuropsychological testing. Nonfocal TNA was defined as one or more of the following transient symptoms: blurry vision, positive visual phenomena, decreased consciousness, confusion, amnesia, unsteadiness, non-rotatory dizziness, paresthesia’s or bilateral weakness of legs. Neuropsychological testing included MMSE, tests on attention, visuospatial function, information processing, language, executive function and memory. We calculated z-scores for the MMSE, each cognitive domain and all domains combined and analyzed the association between non-focal TNAs and cognition with linear regression analysis, adjusted for age and education level. Results Twenty-four patients (45%) had experienced one or more non-focal TNAs in the preceding six months. Patients with non-focal TNAs had a lower MMSE (mean 26.9, SD 3.0; 95% CI -.29 tot 2.32) than those without non-focal TNAs (mean 27.9, SD 1.7), but we found no differences in z-scores based on neuropsychological testing, either by domain or overall. After adjustment for age and level of education the association between non-focal TNAs and MMSE remained (bèta= 1.21, 95% CI -2.31 to -.13, p = .03) Conclusions In patients with carotid occlusive disease, non-focal TNAs are associated with a lower MMSE, but not with impairment in specific cognitive domains.

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Abstract 35 – abstract only Strooistraling en huid-intree dosis; Mini C-boog versus C-boog in een fantoom model. Juliaan van Rappard (1), Tijmen de Jong (1), Willy Hummel (2), Chantal Mouës-Vink (1). (1) Afdeling Plastische Chirurgie, Medisch Centrum Leeuwarden (2) Klinisch Fysicus, Medisch Centrum Leeuwarden

Inleiding Het peroperatief gebruik van röntgen doorlichting met de mini C-boog heeft binnen de plastische chirurgie reeds jaren een vaste plek gekregen binnen het chirurgisch armentarium. De mini C-boog is kleiner dan de conventionele C-boog, kan door de chirurg zelf bediend worden en geeft een betere beeldkwaliteit tijdens het doorlichten van kleine ossale structuren. Dit maakt de mini C-boog uitermate geschikt voor gebruik in de hand- en polschirurgie. In dit onderzoek worden de hoeveelheid strooistraling en de huid-intree dosis vergeleken tussen de mini C-boog en de conventionele C-boog. Methode Tijdens het doorlichten van een perspex handfantoom met een mini C-boog (OrthoscanHD, flat-panel) en een C-boog (VeradiusNeo, Philips) werd de strooistraling en huid-intrede dosis gemeten. Het perspex handfantoom werd op een arm tafel geplaatst, direct boven de detector. De strooistraling is gemeten met een 500cc ionisatiekamer; op zeven locaties rondom en op twee verschillende hoogtes (13cm op 90 graden en 20cm op 135 graden ten opzichte van de primaire bundel). Huid-intree dosis is gemeten met een 15cc ionisatiekamer die midden op de arm tafel werd gepositioneerd. Per positie is gedurende 30 seconde gemeten en iedere meting is tien keer herhaald. Resultaat De gemiddelde strooistraling gemeten op beide hoogtes was significant hoger (p<0.05) voor de mini C-boog ten opzichte van de C-boog (respectievelijk 90 graden positie; 12.06 uGy/30s (SD +/-2.98) versus 4.17 uGy/30s (SD +/-0.23) en 135 graden positie; 9.52 uGy/30s (SD +/-0.47) versus 2.79 uGy/30s (SD +/-0.34)). Huid-intree dosis was eveneens significant hoger (p<0.05) bij de mini C-boog, gemiddeld 0.528 mGy/30s (SD +/-0.011) versus 0.0490 mGy/30s (SD +/-0.001) bij de C-boog. Conclusie De Resultaten laten zien dat strooistraling afkomstig van de mini C-boog gemiddeld 3x hoger is vergeleken met de C-boog. De huid-intree dosis is ongeveer 10x hoger bij het gebruik van de mini C-boog. Het advies tot veilig gebruik van de mini C-boog, zoals het beperken van de doorlichtingstijd, het vermijden van de directe stralingsbundel op de handen van de chirurg en het dragen van loodbescherming, wordt hiermee bevestigd.

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Abstract 36 – abstract only PERC rule should be used with caution to rule out pulmonary embolism in patients with a low Wells score. J.M.G. Theunissen (1), C. Scholing (1), W.E. van Hasselt (1), E. ter Avest (1). (1) Department of Emergency Medicine, Medical Centre Leeuwarden, the Netherlands

Background The pulmonary embolism rule-out criteria (PERC) rule is an eight-factor decision rule to support the decision not to order a diagnostic test when the gestalt based clinical suspicion on pulmonary embolism (PE) is low. Objective In the present study, we investigate if the Wells score can be used as a substitute to gestalt in order to quantify clinical suspicion and thereby identify subjects in which the PERC rule can be applied. Methods In a retrospective cohort study, we determined the accuracy of a negative PERC (0) in patients with a low Wells score (<2) to rule out venous thromboembolism (VTE), and compared this to the accuracy of the default algorithm used in our hospital (a low Wells score in combination with a negative D-dimer). Results During the study period, 377 patients were included. Computed tomography pulmonary angiography (CTPA) was performed in 86 patients, and VQ-scintigraphy in one patient. VTE was diagnosed in 18 patients. 78 patients (21%) had a negative PERC score. When further diagnostic studies would have been omitted in these patient, 2 VTE’s would have been missed, resulting in a sensitivity of 89 % (64-98%), and a negative likelihoodratio (LR-) of 0,52 (0,14-1,97). Sensitivity of the default algorithm to exclude VTE was higher: 95% (71-99%) with a negative likelihoodratio (LR-) of 0.25 (0.04-1,73).

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Abstract 37 – abstract only Clinical Manifestation and Correlating Serum Levels of Toxicity with Internet-Purchased Phenibut (β-phenyl-γ-aminobutyric acid). M.L. Toren-Wielema (1), A. Visser (2), N. Bruins (3), E.N. Van Roon (1,4). (1) Dept. of Clinical Pharmacy & Pharmacology, Medical Center Leeuwarden, Leeuwarden (2) Emergency Dept., Medical Center Leeuwarden, Leeuwarden (3) Dept. of Intensive Care, Medical Center Leeuwarden, Leeuwarden (4) Dept. of Pharmacotherapy & Pharmaceutical Care, University Center for Pharmacy, University of Groningen, Groningen

Background Phenibut (β-phenyl-γ-aminobutyric acid) is a GABA-analog structurally similar to baclofen, used in Russia as a prescription drug for its reportedly anxiolytic and cognition enhancing effects. In Western countries, Phenibut can easily be purchased on the Internet as a dietary supplement. Following (supra)therapeutic Phenibut use, central nervous system effects may occur resulting from activation of GABA-receptors, and stimulation of dopamine and serotonin neurotransmission. We report a case of a patient who presented to the Emergency Department (ED) suffering from severe Phenibut toxicity, requiring management on the Intensive Care Unit (ICU). We report the first case of Phenibut poisoning with focus on the association between serum Phenibut concentrations and correlating clinical manifestation. Case details A 34-year-old man with a history of substance addiction presented to the ED in a delirious state with increasing uncontrollable motoric restlessness interspersed with episodes of unconsciousness. At a previous admission with similar clinical presentation, the patient had confessed to having ingested 10 grams of Phenibut. The patient was admitted to the ICU with a Glasgow Coma Scale (GCS) score of 3. During admission, only supportive care was required and blood samples were collected regularly over night. As laboratory testing indicated no intoxication with other substances, a liquid chromatography-mass spectrometry method was developed for the identification and quantification of serum Phenibut concentrations. Despite declining serum levels (54 to 26 mg/L in 5..5. hours, ~1 half-life), the patient’s GCS score alternated between 3 and 7-11, and he continued to demonstrate motoric restlessness and delirious behaviour when awake. After 11.5. hours, the patient’s consciousness had improved to a maximum GCS score. On transferral to the internal ward, the patient was prescribed lorazepam and haloperidol for management of dystonia and delirium. He was discharged the day after in stable condition, not requiring medication.

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Conclusions Phenibut toxicity appears to manifest in fluctuating episodes of agitated delirium with dystonia and sedation. Serum concentration analysis failed to show a clear association between serum concentrations and improving clinical manifestation during the first 10 hours after ICU admission. This case report highlights the dangers of this readily available drug, which can not be detected with routine toxicological testing.

Abstract 38 – abstract only Association between miscarriage and cardiovascular disease in a Scottish cohort. M.M. Wagner (1,2), S. Bhattacharya (3), J. Visser (1), P.C. Hannaford (4), K.W.M. Bloemenkamp (1). (1) Department of Obstetrics, LUMC, Leiden (2) Department of Obstetrics and Gynaecology, MCL, Leeuwarden (3) Epidemiology Group, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland. (4) Centre of Academic Primary Care, Institute of Applied Health Sciences, University of Aberdeen, Scotland

Background Globally, cardiovascular disease is a major cause of premature mortality in women. There is increasing evidence that women with adverse pregnancy outcomes are at increased risk of cardiovascular disease. Aim To assess if miscarriage, whether consecutive or not, is associated with an increased risk of subsequent cardiovascular disease. Methods A cohort study was performed using women with at least one miscarriage or live birth recorded from 1950 - 2010 in the Aberdeen Maternity and Neonatal Databank. The exposed groups consisted of women with non-consecutive, two consecutive or ≥ three consecutive miscarriages; the unexposed group consisted of all women with at least one live birth and no miscarriages. Women were linked to Scottish Morbidity Records for hospital admissions for cardiovascular conditions, cardiac surgery and death registrations. Main outcome measures were ischemic heart disease, cerebrovascular disease and a composite outcome of any disease of circulatory system. A sensitivity analysis was performed dividing the women into those who had one, two or ≥ three miscarriages irrespective of these were consecutive or not.

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Results After excluding women with pre-existing hypertension, type one diabetes mellitus, kidney disease and ‘disease of circulatory system’, 60105 women were analysed; 9419 with non-, 940 with two, 167 with ≥ three consecutive miscarriages and 49579 with no miscarriage. In the multivariate analyses a significant association was found between ischemic heart disease and women with two {Hazard Ratios (HR) 1.75 (95% confidence interval (CI) 1.22-2.52-1.72)} or ≥ three {HR 3.18 (95%CI 1.49-6.804.51)} consecutive miscarriages. Similar patterns of risk were observed in the sensitivity analysis. Conclusions Women with a history of two or more miscarriages, irrespective of whether consecutive or not, appear to have an increased risk of ischemic heart disease.

Abstract 39 – abstract only Increased cardiovascular disease risk in women with a history of recurrent miscarriage. M. M. Wagner (1,2), M. Beshay (1), S Rooijakkers (1), W. Hermes (1), prof. J.W. Jukema (3), S. le Cessie (4), prof. C.J.M. de Groot (5.), prof. J.M.M. van Lith (1), K.W.M. Bloemenkamp (1). (1) Department of Obstetrics, LUMC, Leiden (2) Department of Obstetrics and Gynaecology, MCL, Leeuwarden (3) Department of Cardiology, LUMC, Leiden (4) Department of Clinical Epidemiology and Department of Medical Statistics, LUMC, Leiden (5) Department of Obstetrics and Gynaecology, VU, Amsterdam

Background Cardiovascular disease is the leading cause of death in women. Observational studies suggest that women with a history of recurrent miscarriage have an increased risk of cardiovascular disease. Aim To determine cardiovascular risk factors and predict the long term cardiovascular risk in women with a history of recurrent miscarriage. Methods Women who visited the recurrent miscarriage clinic at Leiden University Medical Centre and had their third consecutive miscarriage below the age of 30 years were invited to participate in this follow-up study between 2012 and 2014, and formed the exposed group. The unexposed group consisted of women with at least one uncomplicated pregnancy and no miscarriage, matched on zip code, age, and date of pregnancy. All women were invited for risk factor screening, including physical examination, urine and blood collection. Main outcome measures were the (extrapolated)10- and 30-year cardiovascular risk scores using the Framingham risk score. A sub analysis was performed for women with idiopathic recurrent miscarriage.

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Results 36 women with recurrent miscarriage and 36 women with no miscarriage were included. Mean follow-up was 7.5. years. Women with recurrent miscarriage had a significantly higher extrapolated 10-year cardiovascular risk score (mean 6.24%, SD 5..44) compared to women with no miscarriage (mean 3.56%, SD 1.82, p=0.007) and a significantly higher 30-year cardiovascular risk score (mean 9.86%, SD 9.10) compared to women with no miscarriage (mean 6.39, SD 4.20, p=0.04), using the Framingham risk score. Calculations in women with idiopathic recurrent miscarriage (n=28) showed similar significant results. Conclusions Women with a history of recurrent miscarriage, irrespective whether idiopathic or not, have an increased risk of cardiovascular disease calculated by Framingham risk scores, compared to women with no miscarriage. More work is needed to find out if women with such a history will benefit from screening and preventative interventions.

Abstract 40 – abstract only E-Health bij mensen met dementie en hun mantelzorgers Resultaten na 1 jaar van geheugenpoli-online.nl S. van der Weide (1) , P.E. van Walderveen (1), G. Wolters (1), E.M.J. van Noort (2). (1) Centrum klinische geriatrie, Medisch Centrum Leeuwarden, Leeuwarden (2) Curavista bv, Geertruidenberg

Achtergrond Na de diagnose dementie start een telefonische medicatie begeleiding. Zo worden bijwerkingen vroeg gesignaleerd. De gesprekken duren 15-20 minuten en roepen ook sociale vragen op. Een nieuwe manier van begeleiding is via online monitoring en e-Consult. Methode De verpleegkundige start het dossier en zorgpad. Galantamine, rivastigmine, memantine en “geen medicatie” zijn verschillende paden. De verpleegkundige autoriseert het behandelteam (geriater en casemanager) in overleg met de patiënt. De patiënt en/of mantelzorger logt in, geeft toestemming, kiest veilige inlogcode en vult het profiel aan. Per zorgpad worden de bijwerkingen uitgevraagd. Daarbij toont het systeem direct wat men zelf kan doen. Bij een ernstige bijwerking, ontvangt de verpleegkundige een alert. De verpleegkundige raadpleegt het dossier en geeft advies via het eConsult of telefoon.

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Resultaten Ten aanzien van het algemeen gebruik: 149 aangemelde personen waarvan 102 (69%) het dossier activeren. Het gebruik bestaat uit: 71 eConsulten, 133 vragenlijsten en 79 raadplegingen van de kennisbank. Ten aanzien van de bijwerkingen: voor 34 personen is een galantamine zorgpad gestart, voor één persoon een memantine zorpad en voor 114 personen geen medicatie zorgpad. In de galantamine groep vulden 17 personen de bijwerkingen in. “bijwerkingen” werden aangegeven door 6 personen na 2 weken, 4 personen na 6 weken en 4 personen na 10 weken. De meerderheid (65%-76%) gaf “géén bijwerkingen” aan. Conclusie Het systeem wordt gebruikt en 65-75% van de mensen die de medicatielijsten invult, meldt geen last te hebben van bijwerkingen. Hierdoor kan het begeleidingsproces efficiënter worden ingericht.

Abstract 41 – abstract only Prevalence of early dumping syndrome after primary roux-en-y gastric bypass. Ragnhild Wijma (1), Marloes Emous (1), Albert Wolthuis (1, 2), Anke Laskewitz (1), Erik Totté (1), André van Beek (2). (1) Medical Centre Leeuwarden, Leeuwarden, The Netherlands (2) University Medical Centre Groningen, Groningen, The Netherlands

Background Although early dumping syndrome is a well-known complication after Roux-en-Y Gastric Bypass (RYGB), data on the long-term prevalence are limited and inconclusive. Aim This study Aims to describes the prevalence of early dumping syndrome in patients 3 to 6 years after primary RYGB, using 3 different criteria. Methods In this cross-sectional study a total of 140 patients after RYGB were randomly selected and approached. Of these, 51 patients agreed to participate in a Mixed-Meal Tolerance Test using a liquid nutrition supplement (Ensure Plus 200ml). The results of the first 28 are presented here. Heart Rate (HR) and Haematocrit (Ht) were measured at baseline and 10, 20, 30 and 60 minutes after the test meal. Symptoms scores were measured at baseline, 30 and 60 minutes. Early dumping was defined as a HR-increase of >10 beats per minute, a Ht-increase of >3%, and/or ≥2 gastrointestinal symptoms and ≥1 vegetative symptom on a symptom score. A confidence interval (CI) was calculated using the Clopper-Pearson method.

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Results Prevalence of early dumping was 84% (n=41) according to HR (95% CI [0,70:0,93]); 31% (n=15) according to Ht (95% CI [0,18:0,45]) and 10% (n=5.) recorded symptom score (95% CI [0,03:0,22]). In the vast majority the objective changes indicative of early dumping occurred within 10 minutes postprandially. Symptoms were reported within 30 minutes postprandially. Conclusions The results show a large discrepancy of the prevalence of early dumping between the different criteria. Hemodynamic evidence of early dumping is only in a few cases accompanied by complaints.

Abstract 42 – abstract only Effect of bisphosphonates on bone mineral density in patients with ankylosing spondylitis in daily clinical practice. J.G. Veneberg (1,2), A. Spoorenberg (1,2), F. Wink (2), R. Bos (2), E. Brouwer (1), E. van der Veer (3), H. Bootsma (1), E.N. van Roon (4), F. Maas (1), S. Arends (1,2). (1) Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen (2) Rheumatology, Medical Center Leeuwarden, Leeuwarden (3) Laboratory Medicine, University Medical Center Groningen, Groningen (4) Clinical Pharmacy and Pharmacology, Medical Center Leeuwarden, Leeuwarden

Background Excessive bone loss can lead to low bone mineral density (BMD) in patients with ankylosing spondylitis (AS). So far, little is known about the effect of treatment with bisphosphonates on BMD in AS. Aim To investigate the effect of bisphosphonates on BMD over 2 years in patients with AS in daily clinical practice. Methods Patients from the Groningen Leeuwarden AS (GLAS) cohort, fulfilling the modified New York criteria for AS, who were treated with bisphosphonates and had 2-year follow-up BMD measurements available were included. All patients were treated with bisphosphonates in combination with calcium and/or vitamin D supplements. Alendronate (70 mg/week) and risedronate (35 mg/week) were used most frequently. BMD of the lumbar spine (anterior-posterior projection at L1-L4) and hip (total proximal femur) were measured using DXA. Wilcoxon-signed rank test was used to compare BMD Z-scores at baseline and after 2 years. The analysis was stratified for the use of TNF-alpha blockers.

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Results In total, 28 patients were included; 68% were male, mean age was 53 +/-14 years, median symptom duration was 20 years (range 1-60), mean BASDAI was 5..1.+/- 2.5., and 82% were HLA-B27 +. Of these patients, 24 (86%) used bisphosphonates during the entire 2-year follow-up within GLAS. Lumbar spine BMD increased significantly from median Z-score of -0.8 at baseline to -0.3 after 2 years of bisphosphonates. Hip BMD increased significantly from -1.1 at baseline to -0.9 after 2 years. In the 18 patients treated with TNF-alpha blockers, lumbar spine and hip BMD increased significantly after 2 years of treatment with bisphosphonates. In the 10 patients without TNF-alpha blocking therapy, only lumbar spine BMD increased significantly after 2 years of bisphosphonates. No differences in BMD change were found between patients who started treatment with bisphosphonates before (n=15) and after inclusion in the GLAS cohort. Conclusions In our observational cohort study, lumbar spine and hip BMD improved significantly during 2 years of treatment with bisphosphonates in patients with AS. This improvement was most pronounced in the lumbar spine of patients who were also treated with TNF-alpha blockers.

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Abstract 43 – abstract only Influence of bariatric surgery on the use of medication. Jan Peter Yska (1), Douwe H. van der Meer (1), Albert R. Dreijer (1), Willeke Eilander (1), Jan A. Apers (2), Marloes Emous (2), Erik R.E. Totté (2), Bob Wilffert (3,4), Eric N. van Roon (1,3). (1) Department of Clinical Pharmacy and Clinical Pharmacology, Medical Centre Leeuwarden, Leeuwarden, The Netherlands (2) Department of Surgery, Medical Centre Leeuwarden, Leeuwarden, The Netherlands (3) Unit of Pharmacotherapy and Pharmaceutical Care, Department of Pharmacy, University of Groningen, Groningen, The Netherlands (4) Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Purpose Bariatric surgery can influence the prevalence and incidence of comorbidities, as well as the pharmacokinetics of drugs. This might lead to changes in the use of drugs. This study aimed to assess the influence of bariatric surgery on the use of medication in patients before and after surgery, focusing on type, number of medications, and daily dosage. Methods In a retrospective and prospective observational study, drug dispensing data from pharmacies of patients undergoing their first bariatric surgery between January 2008 and September 2011 was collected. Dispensing data from 1 month before until 12 months after surgery was analyzed. Drugs were classified according to the WHO-ATC classification system. Dosages of drugs were compared using defined daily dose (DDD). Results Among 450 patients 12 months after surgery, the mean number of drugs per patient for antidiabetics, drugs acting on the cardiovascular system, anti-inflammatory and antirheumatic drugs, and drugs for obstructed airway diseases decreased by, respectively 71.3.% (95 % CI 57.2 to 85.4), 34.5. % (95 % CI 28.2 to 43.0), 45.5. % (95 % CI 13.3 to 72.6) and 33.1.% (95 % CI 15.3 to 53.2). Patients used lower median DDD of oral antidiabetics, beta-blocking agents, and lipid-modifying drugs. Conclusions For some major drug classes 12 months after bariatric surgery, the use of drugs decreases in terms of mean number per patient. A reduction in dose intensity was observed for oral antidiabetics, betablocking agents, and lipid-modifying drugs. Dispensing data from pharmacies may provide detailed information on the use of medications by patients after bariatric surgery.

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Abstract 44 – abstract only Remission of type 2 diabetes mellitus in patients after different types of bariatric surgery: a population-based cohort study in the United Kingdom. Jan Peter Yska (1), Eric N. van Roon (1,2), Anthonius de Boer (3), Hubert G.M. Leufkens (3), Bob Wilffert (2,4), Loek J.M. de Heide (5), Frank de Vries (3,6,7,8), Arief Lalmohamed (3,9). (1) Department of Clinical Pharmacy and Clinical Pharmacology, Medical Centre Leeuwarden (2) Unit of Pharmacotherapy and Pharmaceutical Care, Department of Pharmacy, University of Groningen (3) Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht University, (4) Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen (5) Department of Internal Medicine, Medical Centre Leeuwarden (6) Care and Public Health Research Institute (CAPHRI), Maastricht (7) MRC Lifecourse Epidemiology Unit, Southampton General Hospital, Southampton, United Kingdom (8) Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre (9) Department of Clinical Pharmacy, University Medical Center Utrecht, The Netherlands

Importance To our knowledge, an observational study on the remission of type 2 diabetes mellitus (T2DM) after different types of bariatric surgery based on data from general practice has not been carried out. Objective To assess the effect of different types of bariatric surgery in patients with T2DM on diabetes remission compared with matched control patients, and the effect of the type of bariatric surgery on improvement of glycemic control and related clinical parameters. Design, Setting, and Participants: A retrospective cohort study conducted from May 2013 to May 2014 within the Clinical Practice Research Datalink involving 2978 patients with a record of bariatric surgery (2005-2012) and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or greater. We identified 569 patients with T2DM and matched them to 1881 patients with diabetes without bariatric surgery. Data on the use of medication and laboratory results were evaluated. Exposure Bariatric surgery, stratified by type of surgery (gastric banding, Roux-en-Y gastric bypass, sleeve gastrectomy, or other/unknown).

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Main Outcome and Measures Remission of T2DM (complete discontinuation of glycemic therapy, accompanied with a subsequently recorded hemoglobin A1c level<6.0%) Results Among patients undergoing bariatric surgery we found a prevalence of 19.1% for T2DM. Per 1000 person years 94.5. diabetes mellitus remissions were found in patients who underwent bariatric surgery, compared with 4.9 diabetes mellitus remissions in matched control patients. Patients with diabetes who underwent bariatric surgery had an 18-fold increased chance for T2DM remission (adjusted relative rate [RR], 17.8; 95% CI, 11.2-28.4), compared with matched control patients. The greatest effect size was observed for gastric bypass (adjusted RR 43.1; 95% CI, 19.7-94.5.), followed by sleeve gastrectomy (adjusted RR, 16.6; 95% CI, 4.7-58.4), and gastric banding (adjusted RR, 6.9; 95% CI, 3.1-15.2). Body mass index and triglyceride, blood glucose, and hemoglobin A1c levels sharply decreased during the first 2 years after bariatric surgery. Conclusions and Relevance Population-based data show that bariatric surgery strongly increases the chance for remission of T2DM,. Gastric bypass and sleeve gastrectomy have a greater effect than gastric banding. Although the risks and possible adverse effects of surgery should be weighed against its benefits, bariatric surgery and, in particular, gastric bypass or sleeve gastrectomy may be considered as new treatment option for type 2 diabetes mellit.

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Adres MCL Academie Henri Dunantweg 2 8901 BR Leeuwarden www.mcl.nl/ mcl-academie