Lipids and apolipoproteins in cardiovascular disease

Lipids and apolipoproteins in cardiovascular disease
PhD ceremony: P.J.W.H. Kappelle, MSc
When: December 14, 2016
Start: 09:00
Where: Academy building RUG
Faculty: Medical Sciences / UMCG
Promotor: prof. dr. B.H.R. (Bruce) Wolffenbuttel


The first part of this thesis describes the role of cholesterol particles and associated proteins, and their role in the development of cardiovascular disease. There seems to be an advantage in determining the balance between good and bad cholesterol, as compared to the separate measures when attempting to predict the development of cardiovascular disease. Certain genes that have an influence on proteins transporting cholesterol from one particle to the other, do not seem to have an effect on the predictive value of these measures. The inhibition of this protein does increase the level of the good cholesterol, but this does not seem to result in any survival benefit.

The second part of this thesis describes the effect of cholesterol lowering agents on different cholesterol particles and associated proteins. Cholesterol lowering agents seem to affect the number of particles less than their cholesterol content. This could lead to a lack of intensive cholesterol treatment when only the cholesterol concentration is considered.

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Thyroid cancer treatment

Thyroid cancer treatment
Long-term effects and new developments
PhD ceremony: Ms E.N. (Esther) Klein Hesselink
When: October 12, 2016
Start: 16:15
Promotor: prof. dr. T.P. Links
Where: Academy building RUG
Faculty: Medical Sciences / UMCG

Thyroid cancer is increasingly common. This is especially the case for differentiated thyroid cancer (DTC), which has a favorable prognosis. Treatment consists of surgical removal of the thyroid gland, radioiodine treatment, and life-long administration of relatively high doses of thyroid hormone. This treatment is effective, but also rather aggressive since it can result in the occurrence of both short- and long-term adverse effects. There used to be little attention for this issue, as cancer-related outcome was less favorable. Nowadays, we see a lot of DTC patients with small tumors who have a near-normal life expectancy. For these patients long-term adverse effects of treatment are very important since they can negatively impact quality of life.

In this thesis we therefore studied the occurrence of long-term effects of DTC treatment. We found that atrial fibrillation (a cardiac rhythm disturbance) and mortality due to cardiovascular diseases are more common in DTC patients as compared to the general population. Furthermore, we found that a part of patients have salivary glands dysfunction following radioiodine treatment. Fortunately, the adverse effects of treatment on bone marrow function were limited.

Furthermore, there is a small group of thyroid cancer patients with more aggressive disease. For these patients, cure is often not achievable. Therefore, we studied the efficacy and toxicity of tyrosine kinase inhibitors (a new class of drugs) that have been studied in these patients. In addition, we studied the hereditary material of several thyroid cancers in an attempt to understand more of thyroid cancer pathogenesis.

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Voorkomen van een Addisonse crisis

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In de afgelopen jaren bleek regelmatig dat mensen met een bijnierziekte verschillende instructies ontvingen van hun behandelaars hoe om te gaan met stress. Dit kan ernstige gevolgen hebben omdat het verwarring veroorzaakt en direct van invloed kan zijn op het welzijn van de patiënt en zijn naasten. Daarom is – onder de paraplu van het BijnierNET – in 2015 een nieuwe uniforme stressinstructie gemaakt, samen met diverse internist-endocrinologen, verpleegkundig specialisten en patiënten, voor die gevallen dat de patiënt thuis of onderweg niet goed wordt en er een bijniercrisis dreigt. Ook vanuit het UMCG is hieraan intensief meegewerkt. De nieuwe stressinstructie is verkrijgbaar via uw behandelend internist-endocrinoloog, maar kan ook gedownload worden via de website van Bijniernet.


Radioactief jodium en speekselklieren

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Effects of radioiodine treatment on salivary gland function in patients with differentiated thyroid carcinoma: a prospective study
Authors: Esther N. Klein Hesselink1, Adrienne H. Brouwers1, Johan R. de Jong1, Anouk N.A. van der Horst-Schrivers1, Rob P. Coppes1, Joop D. Lefrandt1, Piet L. Jager2, Arjan Vissink1 and Thera P. Links1
1 University of Groningen, University Medical Center Groningen, Netherlands;
2 Isala Hospital, Zwolle
For correspondence or reprints contact: Thera P. Links, University of Groningen, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.001, Groningen 9700 RB, Netherlands. E-mail:

Introduction: Complaints of a dry mouth (xerostomia) and sialoadenitis are frequent side effects of radioiodine treatment in differentiated thyroid cancer (DTC) patients. However, detailed prospective data on alterations in salivary gland functioning after radioiodine treatment (131I) are scarce. Therefore, the primary aim of this study was to prospectively assess the effect of high-activity radioiodine treatment on stimulated whole saliva flow rate. Secondary aims were to study unstimulated whole and stimulated glandular (i.e., parotid and submandibular) saliva flow rate and composition alterations, development of xerostomia, characteristics of patients at risk for salivary gland dysfunction, and whether radioiodine uptake in salivary glands on diagnostic scans correlates to flow rate alterations.
Methods: In a multicenter prospective study, whole and glandular saliva were collected both before and five months after radioiodine treatment. Furthermore, patients completed the validated xerostomia inventory (XI). Alterations in salivary flow rate, composition and XI score were analyzed. Salivary gland radioiodine uptake on diagnostic scans was correlated with saliva flow rate changes after radioiodine treatment.
Results: Sixty-seven patients (mean age 48±17 years, 63% female, 84% underwent ablation therapy) completed both study visits. Stimulated whole saliva flow rate decreased after ablation therapy (from 0.92 [IQR 0.74-1.25] to 0.80 [0.58-1.18] ml/min, P = .003), as well as unstimulated whole- and stimulated glandular flow rates (p<.05). The concentration of salivary electrolytes was similar at both study visits, whereas the output of proteins, especially amylase (p<.05), was decreased. The subjective feeling of dry mouth increased (P = 0.001). Alterations in saliva flow rate were not associated with (semi)-quantitatively assessed radioiodine uptake in salivary glands on diagnostic scans. For the small cohort of patients undergoing repeat radioiodine therapy, we could not demonstrate alterations in salivary parameters.
Conclusion: We prospectively showed that salivary gland function is affected after high-activity radioiodine ablation therapy in patients with DTC. Therefore, more emphasis should be placed on salivary gland dysfunction during follow-up for DTC patients receiving high-activity radioiodine treatment.



Behandeling met GLP1-receptor agonist kosten-effectief

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The cost-effectiveness of exenatide twice daily (BID) versus insulin lispro three times daily (TID) as add-on therapy to titrated insulin glargine in patients with type 2 diabetes
Authors: J. Gordon, P. McEwan, U. Sabale, B. Kartman & B.H.R Wolffenbuttel

Objective: To evaluate the cost-effectiveness of exenatide twice daily (BID) versus bolus insulin lispro three times daily (TID) as add-on therapy when glycemic control is suboptimal with titrated basal insulin glargine and metformin.
Methods: The analysis was based on the recent 4B Study, which compared exenatide BID and lispro TID as add-on therapies in subjects with type 2 diabetes insufficiently controlled despite titrated insulin glargine. The Cardiff Diabetes Model was used to simulate patient costs and health benefits beyond the 4B Study. The Swedish healthcare perspective was adopted for this analysis; costs are reported in €EUR to aid interpretation. The main outcome measure was the cost per quality-adjusted life-year (QALY) gained with exenatide BID compared to lispro TID.
Results: Exenatide BID was associated with an incremental cost of €1,270 and a QALY increase of +0.64 compared with lispro TID over 40 years. The cost per QALY gained with exenatide BID compared with lispro TID was €1,971, which is within conventional limits of cost-effectiveness. Cost-effectiveness results were generally robust to alternative assumptions and values for key model parameters.
Limitations: Extrapolation of trial data over the longer term can be influenced by modelling and parameter uncertainty. Cost-effectiveness results were generally insensitive to alternative values of key model input parameters and across scenarios.
Conclusions: The addition of exenatide BID rather than insulin lispro to basal insulin is associated with similar or better clinical outcomes. Illustrated from the Swedish healthcare perspective, analysis with the Cardiff Diabetes Model demonstrated that exenatide BID represents a cost-effective treatment alternative to lispro TID as add-on therapy in type 2 diabetes patients insufficiently controlled on basal insulin.



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