In this thesis we examined patient readiness for shared decision making (SDM) about treatment. We first assessed associations between patient-related characteristics and the occurrence of SDM.... Show moreIn this thesis we examined patient readiness for shared decision making (SDM) about treatment. We first assessed associations between patient-related characteristics and the occurrence of SDM. Overall, we did not find consistent associations between characteristics such as age or education level, and the extent to which SDM occurred (measured from the perspective of patients, clinicians, or observers). Second, we assessed what patients need to be ready, i.e., enabled and well-equipped, to participate in SDM about treatment. We identified a wide range of skills, cognitions, and emotions. For instance, patients need to be able to understand the relevant information, be able to and dare to express themselves in consultations with clinicians, and experience an adequate amount of time to talk to clinicians and to consider the options. Finally, we developed a questionnaire, the ReadySDM. The aim of the ReadySDM is to retrospectively measure the extent to which patients felt ready for SDM during a treatment decision-making process. The questionnaire has the potential to identify novel insights into patients’ support needs and ways to enhance SDM in daily practice. Show less
A strong correlation exists between abdominal aortopathy and atherosclerosis. In thoracic aortopathy however, the prevalence of atherosclerosis and its role in the etiology of thoracic aortopathy... Show moreA strong correlation exists between abdominal aortopathy and atherosclerosis. In thoracic aortopathy however, the prevalence of atherosclerosis and its role in the etiology of thoracic aortopathy remained unknown. This thesis therefore studied the cardiovascular disease burden within this patient group. These results showed that the prevalence of atherosclerosis (i.e. cardiovascular disease burden), in contrast to abdominal aortopathy, is not increased within the thoracic aortopathy population. Show less
Thromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it... Show moreThromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it at the same time increases risk of bleeding. With nationwide data from Statistics Netherlands, antithrombotic therapy and relevant clinical outcomes were comprehensively examined in the patient population of atrial fibrillation, overall or among those with comorbid cancer. The results suggest the patient population was increasingly receiving anticoagulants, driven by the newly introduced medication- direct oral anticoagulant and guided by the CHA2DS2-VASc score, and meanwhile the patient population experienced fewer ischemic stroke and major bleeding. In spite of these promising changes, suboptimal medication adherence and potential underuse of anticoagulants remain directions for further improvement. Antithrombotic agent use during pregnancy was also examined in the general Dutch pregnant population, which featured a surge in antiplatelet prescriptions, and risk of preeclampsia/eclampsia decreased and several newborn outcomes improved simultaneously. Together, the studies presented in this thesis provide an overview of antithrombotic therapy in the Netherlands in recent years, providing insights for further improving this treatment and relevant patient outcomes. Show less
Drug candidates with a covalent binding mode have gained interest since the approval of multiple covalent anticancer drugs, but were long avoided due to concerns regarding promiscuous reactivity... Show moreDrug candidates with a covalent binding mode have gained interest since the approval of multiple covalent anticancer drugs, but were long avoided due to concerns regarding promiscuous reactivity with off-target proteins. In this dissertation, the scope and versatility of the newly discovered in situ thiol–alkyne reaction is evaluated: the nonactivated alkynes exhibit an unprecedented target reactivity with excellent thiol selectivity, thus potentially outperforming currently used cysteine-reactive warheads. Chapter 1 starts with the history of (ir)reversible covalent inhibition, the reactivity of (non)activated alkynes, and the serendipitous discovery of the thiol–alkyne reaction. Established technologies for direct detection of covalent protein–drug adducts are reviewed in Chapter 2, and in Chapter 3 a detailed guide for the evaluation of (ir)reversible covalent inhibitors to obtain relevant kinetic parameters is provided, accompanied by kinetic simulations and step-wise protocols for enzymatic activity assays. In Chapter 4, the nitrile warhead in reversible CatK inhibitor odanacatib (ODN) is replaced with alkyne warheads to investigate whether it an irreversible covalent adduct is formed with cysteine protease cathepsin K (CatK) despite having a small recognition element. In Chapter 5, we evaluate if nonactivated alkynes can target noncatalytic cysteine residues by replacing the irreversible covalent acrylamide warhead in EGFR/HER2 inhibitor neratinib by an alkyne warhead. In Chapter 6, the impact of substituents on the alkyne warhead is explored using a panel of ubiquitin-based ABPs bearing substituents on the propargylamide warhead. Finally, the most important findings are summarized in Chapter 7, and placed in the context of covalent drug discovery. Show less
Palliative care is care improving the quality of life of patients and their families, who are facing a life-threatening condition or frailty, through prevention and relief of suffering by means of... Show morePalliative care is care improving the quality of life of patients and their families, who are facing a life-threatening condition or frailty, through prevention and relief of suffering by means of early identification and careful assessment, and treatment of problems of a physical, psychological, social, and spiritual nature. This thesis describes five studies that evaluated the support of clinicians not specialized in palliative care, or generalists in palliative care. The results show that generalists need education on basic palliative care principles and need support with the initiation of a palliative care approach on time, especially when they care for patients with life-limiting illness other than cancer. To have mor attention for alle problems in the physical, psychological, social and spiritual dimension of care, they can be supported with a more structured approach to the total burden of symptoms and problems. This could be achieved by supporting them with a clinical decision support system for symptom management in palliative care. Such a system can be used for every individual patient, includes a symptom predictor, and provides recommendations on treatment and referral possibilities. Show less
Mental health problems among children and youths are common and have numerous negative consequences for young people and their social network. Therewith, these problems pose a social issue. GPs... Show moreMental health problems among children and youths are common and have numerous negative consequences for young people and their social network. Therewith, these problems pose a social issue. GPs play an important role in early detection and management of these problems. Insight into their clinical decision- making and, as a result, way of working would be helpful to develop methods for providing children and youths with the help they need. Previous literature suggest many doctors(-to-be), of whom some are or will become GPs, have (lived) experience related to mental health problems themselves. Previous studies also suggest having (lived) experience influences GPs’ clinical decision-making, and consequently their way of working. It would have clinical benefits for GPs and patients to explore this process. This thesis is constructed of four different articles, each contributing to answering the main question: ‘How do GPs decide on child and youth mental health problems and what is the influence of their(lived) experience regarding these problems on this decision?’ Article 1: How do GPs make decisions regarding mental health problems in children and youths? For answering this subquestion, a mixed methods design was used: interviews among 14 and an online survey among 15 GPs. GPs were asked about their clinical decision-making process on children and youths with mental health problems using three vignettes describing children and youths with mental health problems representative of clinical practice. The findings suggest GPs differ with regards to their decision- making regarding child and youth mental health problems, and that their decision-making is influenced by factors related to 1) the GP, for example if the GP approaches the problem somatically or psychosocially, if the GP considers themself competent enough to solve the problem with regards to their interest in and knowledge about youth mental health care, 2) the child and its social context, for example if the child or youth has psychiatric (co)morbidity, if the problem is likely to solve itself and if the problem could be assessed as being complex and 3) the GPs’ collaboration with other youth care providers, for example if GPs have existing collaboration agreements with these youth care providers and how they view their collaboration. Article 2: Can GPs’ decisions on child and youth mental health problems be supported by means of a decision-support method?For answering this subquestion, a literature search was conducted to retrieve studies that involved clinical decision support methods for GPs’ clinical decision-making related to mental health problems among children and youths. This systematic review yielded 25 studies on 18 clinical decision-support methods, divided into computer-based methods (such as MyGRaCE), telecommunication methods (such as CAP PC) and methods with a combination of components related to computer-based methods and telecommunication methods (such as Collaborative care for depression intervention). The article provides insight into (possible) beneficial clinical implications of clinical decision-support methods. These methods could give more insight into possible mental health problems, they could provide structured information which can be used by the GP and/or parents during their next consultation with the child or youth, and they could also decrease time and costs spent by the primary care practice and the GP. There are also less beneficial clinical implications, such as an inability for some computer-based methods to be used in emergency situations, when time is short, problems for children and youths when using computer-based methods because of their mental status, and impediment to discuss certain topics freely because the decision-support method gives too much direction to the consultation. The article describes certain considerations for GPs when choosing a decision-support method, which may indirectly have a positive impact on the implementation of such methods into general practice. For example, the GP can take into account their way of working, user flexibility of the method for the GP, the child/youth and their parent(s) with regards to understandability and ease of use, if the GP already uses a clinical decision-support method, if the GP already has collaboration agreements with youth care providers, as well as their own attitude and knowledge regarding mental health problems among children and youths.Article 3: Do doctors-to-be, among whom future GPs, have (lived) experience regarding mental health problems? Study focused on preclinical medical students.For answering this subquestion, self-report questionnaires were sent to 1311 preclinical medical students of Leiden University Medical Center to measure burnout-, depression- and anxiety-related symptoms. The article concludes that symptoms related to mental health problems are common among preclinical medical students. Burnout-related symptoms were found in 46%, depression-related symptoms in 27% and anxiety- related symptoms in 29% of preclinical medical students. Burnout-related symptoms among preclinical medical students were correlated with a sleep duration of less than 6 hours per night, low happiness and a high need for recovery after a day of study. Depression- and anxiety-related symptoms were mainly correlated with low optimism, low happiness, and a high need for recovery after a day of study. These findings suggest preclinical medical students are at risk to develop mental health problems, which can inspire universities to come up with preventive interventions.Article 4: Do doctors-to-be, among whom future GPs, have (lived) experience regarding mental health problems? Study focused on medical interns.For answering this subquestion, self-report questionnaires were sent to 709 medical interns of the same institution mentioned in article 3 to measure burnout-related symptoms. Burnout-related symptoms were found in 30% of medical interns. Burnout-related symptoms among medical interns were related to low dedication with regards to work, a high work pace and quantity, a high need for recovery after a day of work and low optimism. These correlates could be used to prevent mental health problems among medical interns by making adjustments to the medical curriculum. The articles of this thesis suggest GPs’ decision-making on mental health problems in children and youths is multifactorial and consists of objective and subjective components. Furthermore, decision-making seems to differ between GPs, which may be an explanation why there are a variety of clinical decision support methods. Some clinical decision support methods have been implemented in the context of research into general practice, like MyGRaCE, CHICA, Mobiletype, Youth StepCare, consultation-liason method(between GPs and psychiatrists), telepsychiatry consultation practice and the MC3 Program. A clinical implication is GPs can choose a decision-support method which match their personal style of clinical decision-making. However, the validity, trustworthiness and usability of available methods need to be further explored. A clinical implication with regards to medical students’ mental health comprises universities provide accessible proactive mental support to preclinical medical interns and medical interns, because many do not seek help themselves. Furthermore, universities could stimulate a stigma-reducing educational environment, for example in collaboration with the department of (Child- and Adolescent) Psychiatry. Therefore, medical students could be equipped with effective strategies to cope with mental health problems. Also, they might be made aware of their vulnerability, so that they may know their subjectivity and use their personal experiences in practice. The results of this thesis invite more (longitudinal) research on the diagnostic precision, predictive value and cost-efficiency of clinical decision-support methods. Furthermore, more research is needed on the prevalence of mental health problems among graduated doctors, like GPs, and possible effects of these problems on their way of working, their decision-making and their contacts with patients. Strengths of this thesis include exploration of a relatively unknown research area, namely GPs’ clinical decision-making regarding mental health problems among children and youths. Therefore, this thesis used multiple research methodologies and it used a practical scope. This thesis also contains several limitations, such as inclusion of a small GP population, as well as self-selection bias in the studies on preclinical medical students, medical interns and GPs. Finally, interpretation of the results of this thesis was impeded because the research has been conducted in one university, because cause and effect of results could not always be disentangled and because of low statistical power. Because having mental health problems may influence GPs’ clinical decision-making, one could explore how (future) doctors work, study and relax. Therefore, it is recommended to strive for educating balanced doctors: persons who, in collaboration with their colleagues, are – through reflection – aware of their needs and wants between professional boundaries. Show less
Adverse drug reactions on sexual functioning (sADRs) may seriously decrease a person's quality of life. This topic is barely discussed in healthcare practice, partly because of little knowledge... Show moreAdverse drug reactions on sexual functioning (sADRs) may seriously decrease a person's quality of life. This topic is barely discussed in healthcare practice, partly because of little knowledge about the association between drugs and sexual function. Research in this thesis supplements this knowledge with quantitative methods, identifying drugs associated with sADRs and taking the first steps in characterizing the population with these drugs in use. In the second part of the thesis, qualitative methods were used to describe the current practice and the potential role of healthcare providers regarding sADRs in primary care, especially in the community pharmacy. With the acquired knowledge, materials have been developed for primary healthcare providers to discuss and agree on local policy about sADRs in their own region. Initial experiences with these materials showed greater awareness of the subject among the healthcare providers concerned. Show less
This thesis contributes to the evidence-base of the influence of patient factors, surgical approach and implant design on outcomes after total hip replacement (THA).A systematic review (SR) shows... Show moreThis thesis contributes to the evidence-base of the influence of patient factors, surgical approach and implant design on outcomes after total hip replacement (THA).A systematic review (SR) shows that there is strong evidence for BMI, age, comorbidity, preoperative functioning and mental health as predictors of physical functioning. A predictive model based on data from this thesis emphasizes preoperative functioning, mental health and pain as predictors.To treat hip fractures, the posterolateral (PLA) and direct lateral surgical approach (DLA) are the most commonly used. The PLA may cause more dislocations, but seems to result in less walking problems and abductor insufficiency than the DLA. All investigated surgical approaches for primary THA resulted in a significant improvement in patient reported outcome measures (PROMs). The anterior and posterolateral approaches provided greater improvement in physical function and pain, but clinical differences were small.A multicenter randomized trial comparing two hip stems is described. No significant difference has been demonstrated between the Collum Femoris Preserving (CFP) and Zweymüller stem in physical function at 5 years or implant survival at 12 years, although CFP may be inferior in cup revisions. A SR suggests lower dislocation rates and revisions for dual mobility cups in THA, but high quality evidence is lacking. Therefore, we designed an RCT comparing dual mobility cups with unipolar cups in older patients.In addition to providing insights into the influence of patient, surgical and implant characteristics on outcome after (total) hip arthroplasty, this thesis provides suggestions for the design of future clinical trials. Show less
The aim of this thesis is to develop noise robust electrical properties tomography (EPT) reconstruction methods that are free from tissue transition artifacts to support clinical applications for... Show moreThe aim of this thesis is to develop noise robust electrical properties tomography (EPT) reconstruction methods that are free from tissue transition artifacts to support clinical applications for complex tissue structures such as the brain. In particular the contrast-source inversion approach is pursued. This focus of this thesis is on the reconstruction of the electrical properties from the transmit field of radiofrequency coils most frequently available in magnetic resonance imaging. Show less
This research concerns the role of metabolic sensor AMPK, which is activated during low energy levels, and known to suppress the activation of some immune cells. I studied how AMPK regulates the... Show moreThis research concerns the role of metabolic sensor AMPK, which is activated during low energy levels, and known to suppress the activation of some immune cells. I studied how AMPK regulates the function of dendritic cells (DCs), immune cells that are key regulators of the adaptive immune response. Key findings include that drug-induced AMPK activation in DCs results in metabolic rewiring that leads to immunosuppressive DCs. Furthermore, we show that the AMPK signaling axis in DCs is important for protection against obesity-induced inflammation, while AMPK in DCs inhibits the anti-tumor immune response and thereby promoting tumor growth. Therefore, AMPK activation in DCs may be a promising strategy for the generation of therapeutic tolerogenic DCs, while AMPK inhibition may be beneficial for DC-based cancer therapies. Together, these findings contribute to a better understanding of AMPK as regulator of immunity and tolerance in dendritic cells. Show less
The thesis assess the robustness of 4D flow MRI for analyzing aortic hemodynamics and valvular flow, as well as exploring the clinical potential of this technique in patients with aortic and... Show moreThe thesis assess the robustness of 4D flow MRI for analyzing aortic hemodynamics and valvular flow, as well as exploring the clinical potential of this technique in patients with aortic and valvular disease. The first part of the thesis evaluates the reproducibility of segmenting the aortic lumen and calculating various hemodynamic parameters, demonstrating that these processes can be performed accurately and consistently. The second part examines the natural course of aortic hemodynamics during aging, concluding that hemodynamic parameters remain relatively stable. Furthermore, different hemodynamic phenotypes are identified in patients with aortic root and ascending aortic dilatation, possibly explaining the presence of dilatation. Show less
Cancer immunotherapy has experienced remarkable advances in the last decades. Striking clinical responses have been achieved for several solid cancers, particularly cancer types with a high... Show moreCancer immunotherapy has experienced remarkable advances in the last decades. Striking clinical responses have been achieved for several solid cancers, particularly cancer types with a high mutation burden, which placed tumour-mutated antigens (neoantigens) centre stage as targets of tumour immunity and cancer immunotherapy. Neoantigens can be presented in complex with HLA molecules on the tumour cell surface, where T cells with the correct specificity can recognize the neoantigen as ‘non-self’ which will trigger killing of the tumour cell by the T cell. In theory, cancers with a low/moderate mutation burden that present neoantigens in complex with HLA class molecules could still be eligible for T cell-mediated immunotherapy. This thesis, describes the finding that neoantigen-specific T cells are present in mismatch-repair proficient (MMR-p) colorectal cancer patients, a low mutation burden cancer type. Moreover, CD39 and CD103 were found as cell surface markers that pinpoint the T cell population that contains the neoantigen-specific T cells. In addition, subsequent metastasis of a melanoma patient cohort were studied and revealed that also at advanced, late-stage disease, neoantigen-directed T cell therapy is, in theory, still applicable. Taken together, the studies reveal potential for the development of neoantigen-directed cancer immunotherapy for a broader patient population. Show less
The endothelium is a crucial component of the vascular system, and its proper function is vital for microcirculatory function and by extension cardiovascular health. Hence, endothelial dysfunction... Show moreThe endothelium is a crucial component of the vascular system, and its proper function is vital for microcirculatory function and by extension cardiovascular health. Hence, endothelial dysfunction is involved in a majority of cardiovascular disease and poses a high societal burden. Endothelial nitric oxide bioavailability is essential for a healthy microcirculation. The first half of this thesis investigates the reliability of imaging techniques that non-invasively assess the microcirculation and nitric oxide bioavailability, including laser speckle contrast imaging, Doppler flowmetry, dark field microscopy, skin fluorescence imaging and near infrared spectroscopy. In addition, the vascular effects of a mixed meal and a far-infrared light emitting patch, as measured with the imaging methods, are assessed. Finally, differences in microcirculatory function in people with mitochondrial disorders and healthy volunteers are explored. In the second half of the thesis, first-in-human and proof-of-mechanism studies with a soluble guanylyl cyclase stimulator and a phosphodiesterase inhibitor are described, drugs thought to enact some of their effects through modulation of vascular function downstream of nitric oxide. The thesis concludes with a critical appraisal of the investigated imaging modalities and their potential for inclusion in future clinical trials with drugs aiming to affect the microcirculation. Show less
Targeted therapy using EGFR inhibitors cetuximab and panitumumab has anti-tumor efficacy in colorectal cancer, though only in patients without a KRAS mutation in their tumor. This thesis aims to... Show moreTargeted therapy using EGFR inhibitors cetuximab and panitumumab has anti-tumor efficacy in colorectal cancer, though only in patients without a KRAS mutation in their tumor. This thesis aims to give insight on several aspects of EGFR inhibitors en RAS mutations in colorectal cancer. It reviews aspects of mutational analysis, aims to find ways to restore sensitivity to EGFR inhibitors in patients with KRAS mutated colorectal cancer and discusses the distinctive skin toxicity of cetuximab en pantiumumab. Show less
Healthcare is under pressure: an ageing population, healthcare-staff shortage, quality (healthcare outcomes) must increase and costs must be reduced.Yet, what are the outcomes of healthcare?For... Show moreHealthcare is under pressure: an ageing population, healthcare-staff shortage, quality (healthcare outcomes) must increase and costs must be reduced.Yet, what are the outcomes of healthcare?For some conditions, quality of care is measured for every patient. Unfortunately, this is not the case for prostate cancer and lumbar disk herniation in the Netherlands. We used claims data to evaluate healthcare outcomes and volume-outcome relationships.Examples of our results:Prostate cancer:• More than 30% of patients is incontinent 1 year after radical prostatectomy• Large differences between hospitals (19%-85%)• Risk of incontinence is 52% lower at highest-volume hospitalsLumbar disk herniation:• One year after hernia surgery, 23% of patients have one or more undesirable outcomes (e.g. re-operation, use of opioids).• Wide variation in number of operations and outcomes per hospitalOur recommendations:• Reconsider the disproportionately strict interpretation of the GDPR (AVG) for healthcare research• Unlock the huge potential of healthcare research based on existing data • Make routine measurement of healthcare outcomes a national standard, for prostate cancer even on a per surgeon level• Centralization of care should be combined with outcome measurement• Hospitals should share healthcare outcomes with patients• Our results urge doctors, health insurers, patient organizations and policymakers to take action Show less
The first aim of this thesis was to evaluate the Late Effects Comprehensive Care & Follow-up (LEEF) program after pediatric stem cell transplantation for nonmalignant diseases at the LUMC, and... Show moreThe first aim of this thesis was to evaluate the Late Effects Comprehensive Care & Follow-up (LEEF) program after pediatric stem cell transplantation for nonmalignant diseases at the LUMC, and includes the assessment of various late effects and health-related quality of life. The second aim was to implement and evaluate aspects of VBHC at the LEEF program. This thesis describes lessons learned from the VBHC implementation in the Late Effects Comprehensive Care & Follow-up (LEEF) program and suggests possible future directions for VBHC implementation in similar comprehensive care programs. In this thesis, patient-reported outcomes (PROs) have demonstrated their value in research, such as long-term quality of life studies, but they have also proven to be valuable when used in clinical practice. The evaluation of PROs for both research purposes and clinical use can be expanded within the broader care path of pediatric stem cell transplantation. Furthermore, when discussing long-term HSCT outcomes, it is not solely about survival rates, but PROs are integral to capturing these long-term outcomes. Show less
Oxygen supplementation is a cornerstone of supportive medical treatment for critically ill patients. We studied self-reported attitudes towards oxygen therapy and actual clinical practice of ICU... Show moreOxygen supplementation is a cornerstone of supportive medical treatment for critically ill patients. We studied self-reported attitudes towards oxygen therapy and actual clinical practice of ICU clinicians. We found that clinicians are concerned with oxygen induced lung injury and will change mechanical ventilation settings accordingly. However, we performed a large, randomized trial assessing whether a conservative oxygenation strategy resulted in reduced mortality compared to a liberal oxygenation strategy and found there was no significant difference in mortality between the two groups. This thesis has brought to light an important problem of studying ICU patients regarding the consent procedure. We had to exclude patients because no consent had been obtained, losing valuable data and risking selection bias. Afterwards we asked patients how they experienced participating in the trial and most were not aware of their participation but did agree with their participation. This challenges the feasibility of informed consent in critically ill patients. Moreover, we researched disturbances in the homeostasis of sodium and found that an increase in serum sodium was associated with mortality, even in patients with normonatremia and moderate hyponatremia. This challenges the assumption that correcting hyponatremia would lead to lower mortality. Show less
This thesis explores the 4 pillars of Primary Healthcare (PC), the innovations that have been implemented to improve them, and the role digital technologies may have had as part of these... Show moreThis thesis explores the 4 pillars of Primary Healthcare (PC), the innovations that have been implemented to improve them, and the role digital technologies may have had as part of these innovations, with a focus on their impact in the management of chronic conditions. This thesis seeks to identify the optimal way to incorporate digital technologies in PC and how they could improve the PC consultation, in particular, and the PC field in general. It is composed of three parts: the first revises the concept of PC and explores interventions to improve it; the second part, delves into the role digital technologies have had in improving PC and looks at how apps may impact the treatment of chronic conditions. And the third, explores the digital competencies required for PC professionals to use these technologies. Show less
Prostate cancer (PCa) is the second most prevalent cancer among men worldwide when assessing age-standardized incidence rates. The primary method for early PCa diagnosis involves measuring the... Show moreProstate cancer (PCa) is the second most prevalent cancer among men worldwide when assessing age-standardized incidence rates. The primary method for early PCa diagnosis involves measuring the serum concentration of prostate-specific antigen (PSA), with elevated levels (> 3 ng/mL in the Netherlands) indicating the potential presence of PCa. However, the conventional PSA test exhibits a low specificity. Thus, clinical challenges persist, including the differentiation between PCa and benign prostatic hyperplasia and distinguishing indolent PCa from aggressive forms. This underscores the need for a more specific biomarker for early PCa detection and stratification. Previous studies have reported altered glycosylation features in two prostate-secreted glycoproteins, PSA and prostatic acid phosphatase (PAP) in PCa patients, e.g. variation in sialylation, fucosylation and the level of LacdiNAc . The aim of this thesis was to identify PCa biomarkers for early detection and to improve patient stratification, focusing specifically on the glycomic profiles of PSA and PAP. In addition, as PSA plays an important role with regard to fertility, its glycosylation -in relation to male infertility- was also touched upon. For this purpose, mass spectrometry (MS) based glycoproteomic methods were established to map the glycoprofiles of PSA and PAP derived from various biofluids. Show less