Hospital Management in a Partly Competitive Environment

Abstract This study investigates the relevant planning & control components for hospitals’ management while the Dutch Healthcare sector is in the transition from not-for profit to (regulated) market competition. For this purpose a conceptual framework focussing on management based on integral results is developed. Subsequently, this model is tested through interviews and meetings with hospitals and other experts in the field. The results indicated that the model principally holds in the selected settings. However, innovative and appropriate components or critical success factors could not be found, suggesting that this thesis, relating to current practice, might still be one bridge too far

Prognostic biomarkers for stage II and III colon cancer

As we learn more and more about the underlying biology of colon cancer, biomarkers will play a prominent role in the improvement of the identification of patients with high risk of recurrence. Once the identification of the prognostic tumour characteristics has been optimized an appropriate therapy can be advised, whereas others may safely choose to refrain from adjuvant therapy. In this thesis we tried to optimize the process of identification of patients with poor prognosis, the efficacy, the safety and the cost-effectiveness of adjuvant therapies need to be addressed separately, and was beyond the scope of this thesis. In Chapter 2 we described the prognostic value of microvessel density (MVD) as a surrogate marker for angiogenesis, one of the hallmarks of cancer. As angiogenesis itself remains difficult to measure directly, MVD may provide insight in this microenvironmental process. This computerized morphological study showed that MVD increases with stage, which may explain the observation that stage II patients with high MVD had poor prognosis, biologically being a kind of pre-stage III. Actual stage III patients with high MVD, that were all treated with adjuvant 5-FU based chemotherapy, showed better prognosis on the contrary. We hypothesized that residual or recurrent tumour tissue in stage III patients, from primary tumours with high MVD, were better penetrable for chemotherapy, explaining the improved survival. In Chapter 3 we tried to validate CDX2 immunohistochemically, being a promising biomarker published in a high-impact journal by Dalerba et al. Our study showed the practical hurdles involved in validating biomarkers in other cohorts. For disease free survival we were not able to find significant differences between high and low expression of CDX2. However, for disease specific survival we did find comparable results. For a subset of 41 patients we analysed expression of CDX2 by both immunohistochemistry and mass spectrometry. Interestingly, discriminatory power of CDX2 as a prognostic biomarker detected by mass spectrometry outperformed the immunohistochemical detection method. This observation shows that in some cases the biomarker itself may be promising, but the method ought to be fine-tuned to benefit from that marker’s full potential. In chapter 4 we presented a new biomarker, obtained from promising research in mice. Expression of KCNQ1 and CD44, both regulated by Wnt-signalling, was analysed immunohistochemically in 386 stage II and III patients, and on mRNA in an external cohort of 90 patients. We concluded that KCNQ1 was a strong prognostic biomarker for disease recurrence. KCNQ1 may be particularly useful in stage II MSS patients, where the question remains which patients are at risk for recurrence and might benefit from adjuvant chemotherapy. In Chapter 5 MACROD2 was discussed, a relatively unknown gene, although a tumour suppressing function by activating PARP1 and DNA repair is suspected. We indeed found that low nuclear expression was associated with poor prognosis in stage III MSS colon cancer patients, treated with 5-FU based ACT. Even more, high expression of MACROD2 may serve as a predictive biomarker in stage III MSS tumours, favouring adjuvant treatment with 5-FU compared to no adjuvant treatment at all. In the final chapter, Chapter 6, we describe an ultimate attempt to improve the identification of high risk patients. Several biomarkers have been studied on our cohort over the years, some with promising and some with disappointing results. For this study we intended to analyse all these markers combined, to find out which (combination of) biomarkers was able to estimate prognosis best, and whether or not previous less important biomarkers became more interesting. Although other techniques were also used on (some subsets of) this cohort, i.e. mass spectrometry, next generation sequencing and morphological analysis (MVD), for this study we chose for a feasible and widely applicable technique like immunohistochemistry. Therefore, all immunohistochemical biomarkers examined previously on tissue micro arrays were included, in addition to all common clinical and pathological parameters available in our cohort. These were all included in a Classification and Regression Tree (CART) analysis, which showed that both lymphovascular invasions (LVI) and KCNQ1 were the key features for estimating prognosis in stage II and III colon cancer

Opportunities for Dutch Biorefineries

Deze Roadmap Bioraffinage beschrijft een aantal mogelijke routes naar de ontwikkeling en implementatie van een bioraffinage-gerelateerde Bio-based Economy in Nederland. De Roadmap combineert korte- en middellange termijn mogelijkheden (commerciële implementatie, demonstratie plants, pilot plants en gerelateerd toegepast onderzoek) met strategisch onderzoek voor de langere termijn. Tevens zijn vier z.g. Moonshots uitgewerkt, als voorziene bioraffinagestrategieën met een grote potentie voor de Nederlandse economi

Financieel-economische aspecten van Biobrandstofproductie : deskstopstudie naar de invloed van co-productie van bio-based producten op de financiële haalbaarheid van biobrandstoffen

Door uitvoering van een deskstop studie heeft WUR, in samenwerking met ECN, onderzocht of co-productie van biobrandstoffen en bio-based producten leidt tot meer marktcompetitieve biobrandstofproductie. De centrale vraagstelling van de studie was of aangetoond kan worden dat “co-productie” resulteert in realisatie van meer marktcompetitieve waardeketens voor grootschalige en duurzame inzet van biomassa in de biobased economy. De studie naar de financiële haalbaarheid van een twaalftal biobrandstofketens laten zien dat co-productie van biobrandstoffen tezamen met bio-based producten een goede methode is om additionele waarde toe te kennen aan de totale biomassa-product-keten. De co-producten die tezamen met biobrandstoffen geproduceerd kunnen worden zijn zeer divers. In het algemeen bestaat er voor deze co-producten een omvangrijke afzetmarkt, en gaat het om producten die op dit moment grotendeels uit aardolie vervaardigd worden. Technologieën voor productie en toepassing van hoogwaardige co-producten die naast biobrandstoffen uit biomassa geproduceerd kunnen worden bevinden zich in verschillende stadia van ontwikkeling

The microcirculation in severe heart failure and cardiogenic shock

This thesis reports characteristics of the microcirculation in cardiogenic shock, as well as approaches to influence microvascular blood flow

Human resource management at the intensive care unit:A pragmatic review and future research agenda for building a learning health system

Recently, the importance of efficient and effective health care has been recognized, especially during the acute phase of the Coronavirus Disease-2019 (COVID-19) pandemic. Intensive care units (ICUs) have faced an immense workload, with massive numbers of patients being treated in a very short period of time. In general, ICUs are required to deliver high-quality care at all times during the year. At the same time, high-quality organizational goals may not be aligned with the interests, motivation, and development of individual staff members (eg, nurses, and doctors). For management of the ICU, it is important to balance the organizational goals and development of the staff members (“their human capital”), usually referred to as human resource management. Although many studies have considered this area, no holistic view of the topic has been presented. Such a holistic view may help leadership and/or other stakeholders at the ICU to design a better learning health system. This pragmatic review aims to provide a conceptual model for the management of ICUs. Future research may also use this conceptual model for studying important factors for designing and understanding human resources in an ICU.</p