Endovascular abdominal aortic aneurysm repair:Evaluation of outcomes and risks of postoperative surveillance

This thesis investigates the outcomes of patients who underwent endovascular aneurysm repair (EVAR) for an abdominal aortic aneurysm (AAA). The use of EVAR has been rapidly increased since the 1990s and is, compared to open surgical repair, less invasive and associated with a significant reduction in perioperative mortality. The potential disadvantage of EVAR is the need for lifelong imaging surveillance to detect endograft related complications. The main focus of this thesis is to establish the rationale behind the current post-EVAR follow-up regimen, and to examine whether the frequency of imaging surveillance can be safely reduced in a certain subgroup of patients. Risk stratification based on the results of the first postoperative imaging study following EVAR may improve patient outcomes, reduce overtreatment and costs, and may increase adherence among patients where strict follow-up is necessary.The first part of this thesis focuses on clinical outcomes in patients with an AAA who underwent EVAR. The purpose of this section is to determine the effectiveness of the current follow-up regimen and to gain insight in how patients experience yearly imaging follow-up. The second part investigates complications and secondary interventions that occur after AAA repair, with the aim of improving postoperative care

De ex-werknemer

Ex-werknemer wordt iemand door het einde van de arbeidsovereenkomst, wat zowel kan gebeuren tijdens als aan het einde van iemands loopbaan. Een ex-werknemer is dus niet per definitie oud en gepensioneerd, maar kan net zo goed een jong iemand zijn die van baan wisselt. Ex-werknemers zijn daardoor een divers gezelschap, met uiteenlopende belangen. Wat zij gemeen hebben is dat zij zich allen in de postcontractuele fase bevinden ten opzichte van hun ex-werkgever. Ik doel daarmee op de voortdurende rechtsverhouding tussen de ex-werknemer en ex-werkgever. Dit onderzoek behandelt hoe in wetgeving en rechtspraak wordt omgegaan met de postcontractuele rechtsverhouding. In dat kader wordt onderzocht wat de postcontractuele rechtsverhouding tussen de ex-werknemer en de ex-werkgever inhoudt, in hoeverre deze rechtsverhouding door het arbeids- en pensioenrecht wordt beheerst en of daaraan behoefte is. De onderliggende vraag is welke bijzondere problemen ontstaan in de postcontractuele rechtsverhouding en hoe die problemen kunnen worden opgelost. De onderwerpen van de postcontractuele rechtsverhouding die in dit onderzoek centraal staan, zijn zorgvuldigheidsverbintenissen, zorg- en beloningsverbintenissen, het wijzigingsvraagstuk en medezeggenschap. Terugkerend thema daarbij is waar de door de wetgever gemaakte keuzes vandaan komen in de verscheidenheid aan wetten die deze onderwerpen bestrijken, hoe de rechter daarmee in de praktijk omgaat en of er een rode lijn in valt te ontdekken

Intensity of mechanical ventilation

The aim of this thesis was to investigate the association of intensity of ventilation with outcome and the predictive value of its markers (i.e. driving pressure and mechanical power) as well as the effects of interventions proposed to decrease the intensity of ventilation, such as the use of automated modes of ventilation and prone positioning, in patients with and without the acute respiratory distress syndrome (ARDS).In the first part of this thesis, we focused on patients without ARDS, in which we found that driving pressure and mechanical power did not increase the predictive validity of regularly used disease severity scores. Furthermore, in patients after cardiac surgery, the use of an automated mode of ventilation decreased the intensity of mechanical ventilation compared to conventional modes of ventilation. Finally, in patients without ARDS mechanical power was shown to have an association with outcome additional to that of its individual components.The second part of this thesis focusses on patients with ARDS. Here we showed that changes in driving pressure caused by prone positioning, although better than other ventilatory parameters, have a poor predictive capacity for mortality. Lastly, in patients with ARDS due to COVID-19 a cumulative exposure to a higher intensity of ventilation was independently associated with worse outcome

Virus genomic epidemiology to inform public health policy:Understanding hepatitis C virus and SARS-CoV-2 transmission in elimination and outbreak settings

The hepatitis C virus (HCV) and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemics have caused global morbidity and mortality. The epidemiology of these two viruses differ extensively, but the genomes of both can be studied to improve our understanding of how they spread locally and internationally. Advances in whole genome sequencing technology in the last decade have revolutionized virus epidemiology: virus genomes are now more readily available for analysis and are an important component of virus surveillance and epidemiology. Virus genomes can help discriminate between local transmission and external introductions and they are used to track the evolution of the virus. In this thesis, we used genomic epidemiological methods to provide insights into HCV transmission among men who have sex with men (MSM) and SARS-CoV-2 transmission patterns in Amsterdam. In the first part of this thesis, we show that HCV elimination among MSM could be complicated due to international transmission clusters and propose an HCV genomic surveillance infrastructure. We also highlight that HCV variants resistant to existing therapies are currently not a threat to elimination, but that resistance should be closely monitored. In the second part of this thesis, we utilized similar methods to describe a SARS-CoV-2 outbreak in a nightclub in Amsterdam and to describe SARS-CoV-2 transmission in the Amsterdam University Medical Centers. This thesis concludes by discussing how results from these studies can be used to guide and inform public health action

Prognostication and local management in bone metastatic disease

This thesis focuses on the prognostication and treatment outcomes in patients suffering from bone metastases in different phases of the disease, which is crucial for the development of optimal screening and treatment plans.In the first part the ability of spine surgeons to estimate the survival of patients with a spinal metastasis (without the use of prediction models) is assessed. Survival time is a crucial factor in the decision making process for these patients. The results of this study show that spine surgeons considerably overestimate a patients ‘survival while estimations do seem to be associated with treatment choice. Algorithms to help physicians in estimating survival may therefor proof to be beneficial. Part II focusses on breast cancer and the association of mutations status of genes TP53 and PIK3CA on metastatic behavior. The results show that TP53 mutates breast cancer has a worse survival but may be less prone to develop bone metastasis. Part III builds on the results of part I, exploring new biomarkers for prognostication of patients with bone metastasis and developing machine learning algorithms to help physicians with survival prediction and thereby decision making for these patients. In the final part of this thesis we look at the (adverse) treatment outcomes of frequently used treatment modalities for patients with a bone metastasis: radiation and surgery. Both modalities have their drawbacks and it is important to carefully weigh the benefits and risks, especially when life expectancy is short

Adult congenital heart disease:When left seems right and right is wrong

Congenital heart disease (CHD) is the most common birth defect and affects approximately 9 per 1,000 newborns. Major advances in the management of children with CHD has yielded a dramatic change in age distribution, with more adults living with CHD nowadays than children. With increased longevity, caregivers need to be prepared to diagnose and treat late complications of this growing and aging patient population, who —in contrast to acquired heart disease— more commonly have right-sided (RV) complications. In this thesis, we addressed the role of the RV in adult CHD in the following clinical settings: in the subpulmonic position in pulmonary arterial hypertension (PAH-CHD), in the subaortic position in transposition of the great arteries (TGA), and when subjected to hemodynamic stress during exercise training.Effective collaborations at both national and international levels have enabled us to challenge the existing paradigm that RV failure is inevitable in CHD. In TGA patients, we observed slow disease progression to end-stage heart failure or death. Several drugs (i.e. selexipag and valsartan) showed less beneficial effects in patients with PAH-CHD or TGA respectively than expected from landmark trials in PAH and LV failure. Exercise training however seemed to be safe, even in those with severe CHD. Lastly, we developed several simplified prediction tools for adverse outcome to help identify those at greatest risk. Better understanding of the risk factors and treatment options for the RV in patients with CHD is highly relevant and must continue to be the focus of intensive research in future

The Dutch pancreatic cancer project:Improving outcome in pancreatic surgery

Pancreatic surgery is complex and carries a high risk of complications. This thesis entitled “The Dutch Pancreatic Cancer Project: improving outcome in pancreatic surgery”, aims to identify factors adding to the improvement of clinical outcome of patients after pancreatic surgery, first by focusing on the reduction of complications (Part I) and secondly by identifying leads to improve survival (Part II).In part I of this thesis, the leakage of pancreatic fluid after pancreatic surgery, i.e. postoperative pancreatic fistula (POPF, i.e. grade B/C), was addressed as the most feared complication in pancreatic surgery. Furthermore, the need for preventive measures was emphasized. In pancreatic cancer patients who received preoperative chemoradiotherapy, the rate of POPF was significantly lower compared to patients after immediate surgery (i.e., without preoperative therapy) after pancreatoduodenectomy. Changes in acinar cell function and pancreatic texture caused by radiotherapy may play a role in this declined risk of POPF. However, preoperative chemoradiotherapy is only indicated for patients undergoing PD for patients with pancreatic cancer, while this thesis concluded that patients with periampullary tumors have a much higher risk of developing POPF. It was hypothesized that a single dose of preoperative radiotherapy targeting the intended site of the pancreatic anastomosis induces local fibrosis of the pancreatic tissue, potentially reducing the risk of pancreatic fistula after pancreatoduodenectomy in patients at high risk of POPF. The FIBROPANC study protocol was presented, in which the safety and feasibility of this hypothesis will be investigated. Additionally, it was concluded that several national efforts have resulted in a significant decrease in in-hospital mortality and an improvement in failure to rescue after pancreatoduodenectomy in the Netherlands.In part II of this thesis, a unified variable list for reporting patient characteristics and outcome measures in randomized trials in patients with pancreatic cancer was presented, enabling better comparison between trials. It was also concluded that the basal-like molecular subtype of pancreatic carcinoma is associated with poor survival after pancreatic resection. In addition, involvement of the para-aortic lymph node station 16b1 is also associated with poor survival in patients with pancreatic or periampullary carcinoma. The role of direct resection in these groups was discussed

Multilingualism and mixed-mode communication:Sociolinguistic insights into the German-Namibian diaspora

Like other disciplines, the field of sociolinguistics is not a homogenous one. It rather comes in three “loosely connected waves” (Eckert 2012) with each wave applying specific sets of methods. How can we use methodological triangulation and combine these methods, both quantitative and qualitative in nature, to integrate the three waves of sociolinguistics? This dissertation focusses on this question through five case studies concerning the German-Namibian diaspora, i.e., German-speaking Namibians who migrated to Germany. Their multilingual repertoire (Standard German, Namdeutsch [Namibian German], English, and Afrikaans) is the main research object. The studies presented in this book use correlational analysis, participant observation and semi-structured interviews to unveil the interplay between extralinguistic variables (e.g., gender, mode, place of origin), individual styles and linguistic variation in both, face-to-face interaction and computer-mediated communication (CMC). In doing so, the dissertation adds the notion of translocalisation to the field of German Sprachinselforschung (research on German-language exclaves). I argue that this notion complements existing perspectives on local and regional dynamics and thus leads to a more holistic view on Sprachinseln. Therefore, this dissertation shows how methodological triangulation offers an opportunity to add new perspectives to already established constructs

SimLex-999 for Dutch

Word embeddings revolutionised natural language processing by effectively representing words as dense vectors. Although many datasets exist to evaluate English embeddings, few cater to Dutch. We developed a Dutch variant of the SimLex-999 word similarity dataset by gathering similarity judgements from 235 native Dutch speakers. Subsequently, we evaluated two popular Dutch language models, Bertje and RobBERT, finding that Bertje showed superior alignment with human semantic similarity judgments compared to RobBERT. This study provides the first intrinsic Dutch word embedding evaluation dataset, which enables accurate assessment of these embeddings and fosters the development of effective Dutch language models