Objectives: Cost-effectiveness analyses typically require measurement of health-related quality of life (HRQoL) to estimate quality-adjusted life-years. Challenges with measuring HRQoL arise in the... Show moreObjectives: Cost-effectiveness analyses typically require measurement of health-related quality of life (HRQoL) to estimate quality-adjusted life-years. Challenges with measuring HRQoL arise in the context of episodic conditions if patients are less likely-or even unable-to complete surveys when having disease symptoms. This article explored whether HRQoL measured at regular time intervals adequately reflects the HRQoL of people with epilepsy (PWE). Methods: Follow-up data from the Epilepsy Support Dog Evaluation study on the (cost-)effectiveness of seizure dogs were used in which HRQoL is measured in 25 PWE with the EQ-5D at baseline and every 3 months thereafter. Seizure count is recorded daily using a seizure diary. Regression models were employed to explore whether PWE were more likely to complete the HRQoL survey on a good day (ie, when seizures are absent or low in frequency compared with other days) and to provide an estimate of the impact of reporting HRQoL on a good day on EQ-5D utility scores. Results: A total of 111 HRQoL measurements were included in the analyses. Regression analyses indicated that the day of reporting HRQoL was associated with a lower seizure count (P,.05) and that a lower seizure count was associated with a higher EQ-5D utility score (P,.05). Conclusions: When HRQoL is measured at regular time intervals, PWE seem more likely to complete these surveys on good days. Consequently, HRQoL might be overestimated in this population. This could lead to underestimation of the effectiveness of treatment and to biased estimates of cost-effectiveness. Show less
This thesis describes the effects of shortterm fasting on chemotherapy outcome in patients with breast cancer and the IGF-1 and insulin pathway as a target for cancer therapy and as a biomarker for... Show moreThis thesis describes the effects of shortterm fasting on chemotherapy outcome in patients with breast cancer and the IGF-1 and insulin pathway as a target for cancer therapy and as a biomarker for chemotherapy outcome.Preclinical research is evaluated, which shows that short-term fasting during chemotherapy is effective. The effects of short-term fasting in humans is not evident yet. Although the first small clinical studies of short-term fasting as adjunct to chemotherapy are promising in terms of decreased toxicity and enhanced efficacy, the exact mechanism and effects are not established yet. More studies and a longer follow-up are needed to prove this.Insulin-like growth factor 1 (IGF-1) and insulin are members of the IGF-1 pathway, which is involved in cell growth and proliferation. The effects of the IGF-1 pathway on chemotherapy outcome and the pathway itself as target for cancer therapy are described. The disappointing results of clinical studies of IGF-1R inhibitors may be caused by the complexity of the IGF-1R pathway. Lowering both insulin and IGF-1, perhaps with a short-term fasting intervention, serves as a possible target in cancer therapy. Show less
Houtsma, D.; Groot, S. de; Baak-Pablo, R.; Kranenbarg, E.M.K.; Seynaeve, C.M.; Velde, C.J.H. van de; ... ; Gelderblom, H. 2021
The PvuII (rs2234693) Single Nucleotide Polymorphism (SNP) in the gene coding for the estrogen receptor-1 (ESR1), has been found associated with outcome in tamoxifen treated patients with early... Show moreThe PvuII (rs2234693) Single Nucleotide Polymorphism (SNP) in the gene coding for the estrogen receptor-1 (ESR1), has been found associated with outcome in tamoxifen treated patients with early hormone-receptor positive breast cancer. However, it remains unclear whether this SNP is a predictive marker for tamoxifen efficacy or a prognostic marker for breast cancer outcome. The aim of this study was to examine the prognostic potential of this SNP in postmenopausal early breast cancer patients treated with adjuvant exemestane. Dutch postmenopausal patients randomised to 5 years of adjuvant exemestane of whom tissue was available (N=807) were selected from the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial database. The SNP rs2234693 in the ESR1 gene was genotyped on DNA from formalin-fixed paraffin embedded (FFPE) tumor tissue using Taqman assays and related to the primary endpoint disease-free survival (DFS) and secondary endpoint overall survival (OS). Survival analyses were performed using Cox regression analysis. In total 805 patients were included in the analyses (median follow up of 5.22 years) and genotypes were obtained in 97% of the samples. The variant T allele of PvuII in ESR1 (rs2234693) was associated with a better DFS (hazard ratio (HR) 0.689, 95% confidence interval (CI) 0.480-0.989, P=0.044) in univariate analysis only, and a better OS in both univariate (HR 0.616, 95%, CI 0.411-0.923, P=0.019) and multivariate analyses (HR 0.571, 95% CI 0.380-0.856, P=0.007), consistent with a prognostic rather than a predictive drug response effect. Variation of PvuII in the ESR1 gene is related to OS in postmenopausal, early HR+breast cancer patients treated with exemestane in the TEAM study. Variation in the ESR1 gene may therefore be a prognostic marker of early breast cancer survival, and warrants further research. Show less
Sinds het begin van de coronacrisis is onze ministerpresident niet meer weg te denken uit het dagelijkse nieuws. Denk aan de vele persconferenties, interviews en debatten. Maar ook de toespraken... Show moreSinds het begin van de coronacrisis is onze ministerpresident niet meer weg te denken uit het dagelijkse nieuws. Denk aan de vele persconferenties, interviews en debatten. Maar ook de toespraken vanuit het torentje en hét persmoment. Soms wordt de minister-president vergezeld door de vakminister en blikvanger Irma Sluis. Het toenemende belang van de rol van de minister-president is historisch lang niet zo vanzelfsprekend geweest, maar past in een ontwikkeling van presidentialisering die al langer is ingezet. Dat is nu extra zichtbaar. In de wetenschappelijke literatuur wordt geschreven over het fenomeen presidentialisering, dat zichtbaar is in meerdere parlementaire democratieën in West-Europa. Er wordt van presidentialisering gesproken als de focus van politiek, publiek en media steeds meer komt op personen en op het ambt van de minister-president zonder dat de formele structuur daarvoor wordt gewijzigd. Het aantal democratieën dat kan worden bestudeerd is niet groot. Er is immers maar een beperkt aantal van 21 volledige democratieën, veel daarvan hebben een presidentieel stelsel waarvoor de theorie van presidentialisering sowieso niet opgaat. Het internationaal onderzoek richt zich dan ook met name op het Verenigd Koninkrijk, Zweden en Denemarken. Maar hoe staat dat in Nederland? En is dit terug te zien in de aanpak van de coronacrisis? Show less
Background: Epilepsy is associated with a high disease burden, impacting the lives of people with epilepsy and their caregivers and family. Persons with medically refractory epilepsy experience the... Show moreBackground: Epilepsy is associated with a high disease burden, impacting the lives of people with epilepsy and their caregivers and family. Persons with medically refractory epilepsy experience the greatest burden, suffering from profound physical, psychological, and social consequences. Anecdotal evidence suggests these persons may benefit from a seizure dog. As the training of a seizure dog is a substantial investment, their accessibility is limited in the absence of collective reimbursement as is seen in the Netherlands. Despite sustained interest in seizure dogs, scientific knowledge on their benefits and costs remains scarce. To substantiate reimbursement decisions stronger evidence is required. The EPISODE study aims to provide this evidence by evaluating the effectiveness and cost-effectiveness of seizure dogs in adults with medically refractory epilepsy.Methods: The study is designed as a stepped wedge randomized controlled trial that compares the use of seizure dogs in addition to usual care, with usual care alone. The study includes adults with epilepsy for whom current treatment options failed to achieve seizure freedom. Seizure frequency of participants should be at least two seizures per week, and the seizures should be associated with a high risk of injury or dysfunction. During the 3 year follow-up period, participants receive a seizure dog in a randomized order. Outcome measures are taken at multiple time points both before and after receiving the seizure dog. Seizure frequency is the primary outcome of the study and will be recorded continuously using a seizure diary. Questionnaires measuring seizure severity, quality of life, well-being, resource use, productivity, social participation, and caregiver burden will be completed at baseline and every 3 months thereafter. The study is designed to include a minimum of 25 participants.Discussion: This protocol describes the first randomized controlled trial on seizure dogs. The study will provide comprehensive data on the effectiveness and cost-effectiveness of seizure dogs in adults with medically refractory epilepsy. Broader benefits of seizure dogs for persons with epilepsy and their caregivers are taken into account, as well as the welfare of the dogs. The findings of the study can be used to inform decision-makers on the reimbursement of seizure dogs. Show less
