PURPOSEDPYD-guided fluoropyrimidine dosing improves patient safety in carriers of DPYD variant alleles. However, the impact on treatment outcome in these patients is largely unknown. Therefore,... Show morePURPOSEDPYD-guided fluoropyrimidine dosing improves patient safety in carriers of DPYD variant alleles. However, the impact on treatment outcome in these patients is largely unknown. Therefore, progression-free survival (PFS) and overall survival (OS) were compared between DPYD variant carriers treated with a reduced dose and DPYD wild-type controls receiving a full fluoropyrimidine dose in a retrospective matched-pair survival analysis.METHODSData from a prospective multicenter study (ClinicalTrials.gov identifier: NCT02324452) in which DPYD variant carriers received a 25% (c.1236G>A and c.2846A>T) or 50% (DPYD*2A and c.1679T>G) reduced dose and data from DPYD variant carriers treated with a similarly reduced dose of fluoropyrimidines identified during routine clinical care were obtained. Each DPYD variant carrier was matched to three DPYD wild-type controls treated with a standard dose. Survival analyses were performed using Kaplan-Meier estimates and Cox regression.RESULTSIn total, 156 DPYD variant carriers and 775 DPYD wild-type controls were available for analysis. Sixty-one c.1236G>A, 25 DPYD*2A, 13 c.2846A>T, and-when pooled-93 DPYD variant carriers could each be matched to three unique DPYD wild-type controls. For pooled DPYD variant carriers, PFS (hazard ratio [HR], 1.23; 95% CI, 1.00 to 1.51; P = .053) and OS (HR, 0.95; 95% CI, 0.75 to 1.51; P = .698) were not negatively affected by DPYD-guided dose individualization. In the subgroup analyses, a shorter PFS (HR, 1.43; 95% CI, 1.10 to 1.86; P = .007) was found in c.1236G>A variant carriers, whereas no differences were found for DPYD*2A and c.2846A>T carriers.CONCLUSIONIn this exploratory analysis, DPYD-guided fluoropyrimidine dosing does not negatively affect PFS and OS in pooled DPYD variant carriers. Close monitoring with early dose modifications based on toxicity is recommended, especially for c.1236G>A carriers receiving a reduced starting dose. Show less
Graaf, J.A. de; Visser-Meily, J.M.; Schepers, V.P.; Baars, A.; Kappelle, L.J.; Passier, P.E.; ... ; Post, M.W. 2021
BACKGROUND: Although the use of patient-reported outcome measures to assess Health-Related Quality of Life (HRQoL) has been advocated, it is still open to debate which patient-reported outcome... Show moreBACKGROUND: Although the use of patient-reported outcome measures to assess Health-Related Quality of Life (HRQoL) has been advocated, it is still open to debate which patient-reported outcome measure should be preferred to evaluate HRQoL after stroke.AIM: To compare the measurement properties (including concurrent validity and discriminant ability) between the 5-dimensional 5-level Euro-Qol (EQ-5D-5L) and the Patient-Reported Outcomes Measurement Information System 10-Question Global Health Short Form (PROMIS-10) to evaluate HRQoL 3 months after stroke.DESIGN: Cross-sectional study.SETTING: Neurology outpatient clinics in 6 Dutch hospitals.POPULATION: The participants 360 consecutive individuals with stroke. Their median age was 71 years, 143 (39.7%) were female and 335 (93.0%) had suffered an ischemic stroke.METHODS: The EQ-5D-5L, PROMIS-10, modified Rankin Scale and two items on experienced decrease in health and activities post-stroke were administered by a stroke nurse or nurse practitioner through a telephone interview 3 months after stroke. The internal consistency, distribution, floor/ceiling effects, inter-correlations and discriminant ability (using the modified Rankin Scale and experienced decrease in health and in activities post-stroke as external anchors) were calculated for both the EQ-5D-5L and PROMIS-10.RESULTS: Ninety-six percent of the participants were living at home and 50.9% experienced minimal or no disabilities (modified Rankin Scale 0-1) 3 months after stroke. A ceiling effect and a non-normal left skewed distribution were observed in the EQ-5D-5L. The PROMIS-10 showed higher internal consistency (alpha=0.90) compared to the EQ-5D-5L (alpha=0.75). Both the EQ-5D-5L and the PROMIS-10 were strongly correlated with the modified Rankin Scale (r=0.62 and 0.60 respectively). The PROMIS-10 showed better discriminant ability in less affected individuals with stroke, whereas the EQ-5D-5L showed slightly better discriminant ability in more affected individuals with stroke.CONCLUSIONS: Both EQ-5D-5L and PROMIS-10 prove to be useful instruments to evaluate HRQoL in patients who are living at home 3 months after stroke.CLINICAL REHABILITATION IMPACT: The clinical rehabilitation impact depended on the setting and underlying goal which patient-reported outcome measure is preferred to evaluate HRQoL 3 months after stroke. The PROMIS-10 should be preferred to detect differences in less affected stroke patients, whereas the EQ-5D-5L provides slightly more information in more affected stroke patients. Show less
Lugtenberg, R.T.; Groot, S. de; Kaptein, A.A.; Fischer, M.J.; Kranenbarg, E.M.K.; Duijm-de Carpentier, M.; ... ; Dutch Breast Canc Res Grp BOOG 2020
Purpose In the phase II DIRECT study a fasting mimicking diet (FMD) improved the clinical response to neoadjuvant chemotherapy as compared to a regular diet. Quality of Life (QoL) and illness... Show morePurpose In the phase II DIRECT study a fasting mimicking diet (FMD) improved the clinical response to neoadjuvant chemotherapy as compared to a regular diet. Quality of Life (QoL) and illness perceptions regarding the possible side effects of chemotherapy and the FMD were secondary outcomes of the trial. Methods 131 patients with HER2-negative stage II/III breast cancer were recruited, of whom 129 were randomly assigned (1:1) to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and the day of neoadjuvant chemotherapy. The European Organisation for Research and Treatment of Cancer (EORTC) questionnaires EORTC-QLQ-C30 and EORTC-QLQ-BR23; the Brief Illness Perception Questionnaire (BIPQ) and the Distress Thermometer were used to assess these outcomes at baseline, halfway chemotherapy, before the last cycle of chemotherapy and 6 months after surgery. Results Overall QoL and distress scores declined during treatment in both arms and returned to baseline values 6 months after surgery. However, patients' perceptions differed slightly over time. In particular, patients receiving the FMD were less concerned and had better understanding of the possible adverse effects of their treatment in comparison with patients on a regular diet. Per-protocol analyses yielded better emotional, physical, role, cognitive and social functioning scores as well as lower fatigue, nausea and insomnia symptom scores for patients adherent to the FMD in comparison with non-adherent patients and patients on their regular diet. Conclusions FMD as an adjunct to neoadjuvant chemotherapy appears to improve certain QoL and illness perception domains in patients with HER2-negative breast cancer. Trialregister ClinicalTrials.gov Identifier: NCT02126449. Show less
Groot, S. de; Lugtenberg, R.T.; Cohen, D.; Welters, M.J.P.; Ehsan, I.; Vreeswijk, M.P.G.; ... ; Dutch Breast Canc Res Grp BOOG 2020
Short-term fasting protects tumor-bearing mice against the toxic effects of chemotherapy while enhancing therapeutic efficacy. We randomized 131 patients with HER2-negative stage II/III breast... Show moreShort-term fasting protects tumor-bearing mice against the toxic effects of chemotherapy while enhancing therapeutic efficacy. We randomized 131 patients with HER2-negative stage II/III breast cancer, without diabetes and a BMI over 18kgm(-2), to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and during neoadjuvant chemotherapy. Here we show that there was no difference in toxicity between both groups, despite the fact that dexamethasone was omitted in the FMD group. A radiologically complete or partial response occurs more often in patients using the FMD (OR 3.168, P=0.039). Moreover, per-protocol analysis reveals that the Miller&Payne 4/5 pathological response, indicating 90-100% tumor-cell loss, is more likely to occur in patients using the FMD (OR 4.109, P=0.016). Also, the FMD significantly curtails chemotherapy-induced DNA damage in T-lymphocytes. These positive findings encourage further exploration of the benefits of fasting/FMD in cancer therapy. Trial number: NCT02126449. Preclinical evidence suggests that a fasting mimicking diet (FMD) can make cancer cells more vulnerable to chemotherapy, while protecting normal cells. In this randomized phase II clinical trial of 131 patients with HER2 negative early stage breast cancer, the authors demonstrate that FMD is safe and enhances the effects of neoadjuvant chemotherapy on radiological and pathological tumor response. Show less
Koster, B.D.; Santegoets, S.J.A.M.; Harting, J.; Baars, A.; Ham, S.M. van; Scheper, R.J.; ... ; Eertwegh, A.J.M. van den 2019
Al 3 jaar zit op de 6e verdieping van de faculteit het Scriptie-atelier voor pedagogiek-studenten. Sinds 1 januari 2007 is het ook open voor alle andere F.S.W.-studenten. Het loopt alleen nog niet... Show moreAl 3 jaar zit op de 6e verdieping van de faculteit het Scriptie-atelier voor pedagogiek-studenten. Sinds 1 januari 2007 is het ook open voor alle andere F.S.W.-studenten. Het loopt alleen nog niet echt storm in het atelier, slechts vier afgevaardigden van de opleiding Bestuurskunde hebben zich ingeschreven. Bestuurskundige Berichten sprak met drs. Kees Nagtegaal. Hij is docent Bestuurskunde en fungeert ook als S.A.M. (Scriptie-atelier Medewerker). Show less
Nederland is ontstaan door het eeuwige gevecht tegen het water. Samenwerking was noodzakelijk om eenieder tegen het water te beschermen. De helft van Nederland ligt ruim 6 meter onder de zeespiegel... Show moreNederland is ontstaan door het eeuwige gevecht tegen het water. Samenwerking was noodzakelijk om eenieder tegen het water te beschermen. De helft van Nederland ligt ruim 6 meter onder de zeespiegel. Meer dan 10 miljoen mensen leven, werken en recreëren zorgeloos in de polder. En ondertussen worden die 10 miljoen mensen bedreigd door steeds extremer wordende weersomstandigheden en dijken die onder achterstallig onderhoud lijden. Moet er een ramp gebeuren voordat er iets gebeurt? Show less
Sinds kort (18 mei 2006) hebben we er op de 3 e etage van onze grijzige FSW een kleurig kamertje bij! Gestyled met rood en paars en uitgerust met zitkussens waar je eens rustig kan bijpraten over... Show moreSinds kort (18 mei 2006) hebben we er op de 3 e etage van onze grijzige FSW een kleurig kamertje bij! Gestyled met rood en paars en uitgerust met zitkussens waar je eens rustig kan bijpraten over de planning van je loopbaan: de Studenten Loopbaan Service FSW. Ik had een interview met loopbaanadviseuse Lieneke Gijsbers. Show less
