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
Epileptic seizures are associated with changes in autonomic function. Ictal asystole, when it leads to syncope, can cause severe traumatic falls. We discovered a new indirect method, based on video... Show moreEpileptic seizures are associated with changes in autonomic function. Ictal asystole, when it leads to syncope, can cause severe traumatic falls. We discovered a new indirect method, based on video, EEG and ECG, to disentangle if vasodilatation was the dominant mechanism behind the syncope. In this group of patients, pacemaker implantation is less helpful. Autonomic manifestations of epilepsy can also help to detect seizures. Our literature review discovered that combining different modalities in one detection device provides higher sensitivity, and personalization of detection algorithms can decrease false alarm rate. We validated a wearable multimodal detection system (NightWatch) on children at home. NightWatch showed high sensitivity for the detection of potentially dangerous nocturnal seizures, reduces caregiver stress and saved costs from a societal perspective. Validation of an automated video detection system showed that this could provide a good alternative for children who cannot tolerate a wearable device.From different qualitative user studies, we concluded that caregivers’ needs for seizure detection vary greatly. Also, the success of device implementation is highly dependent on the protective behavior parents developed towards their child with epilepsy. This emphasizes the importance of tailored and user-centered approaches for seizure detection. Show less
The focus of this thesis is the improvement of diagnosis, early detection and treatment of CD in children. Increased knowledge, available guidelines and reliable diagnostics allow for timely... Show moreThe focus of this thesis is the improvement of diagnosis, early detection and treatment of CD in children. Increased knowledge, available guidelines and reliable diagnostics allow for timely diagnosis which can prevent complications and improve QoL, but the current healthcare approach is often unable to make the diagnosis in a timely manner. Moreover, despite timely diagnosis and effective therapy, there is a need to improve the follow up. Show less
Children with immune thrombocytopenia (ITP) show a primary hemostasis defect due to reduced number of platelets (thrombocytopenia). This leads to bleeding. In children, ITP is often transient and... Show moreChildren with immune thrombocytopenia (ITP) show a primary hemostasis defect due to reduced number of platelets (thrombocytopenia). This leads to bleeding. In children, ITP is often transient and self-limiting (transient ITP), but some children show persistent thrombocytopenia or even chronic ITP. Treatment with immune-modulating medication like intravenous immunoglobulins (IVIg) leads to early recovery from thrombocytopenia and prevents bleeding. Unfortunately, treatment is only effective in a part of the patients. This dissertation aims to better understand, explain, and predict spontaneous recovery and favorable treatment outcomes after IVIg in a specific child with ITP. To that end, molecular disease mechanisms are being evaluated and analyzed together with clinical data. The dissertation provides novel data working towards individualized care for children with ITP. This is relevant for communication with the child and caregivers over the expected prognosis, treatment decisions (IVIg), and indications for early additional diagnostic testing for other causes of thrombocytopenia (such as genetic tests). Show less
Although clinical aspects of melanoma have been extensively studied, the literature largely concerns relatively healthy 20-70 years old patients. Special populations, such as the elderly, children,... Show moreAlthough clinical aspects of melanoma have been extensively studied, the literature largely concerns relatively healthy 20-70 years old patients. Special populations, such as the elderly, children, patients with multiple primary melanoma and those with familial melanoma, are frequently excluded from clinical studies. The studies presented in this thesis were aimed to assess prognostic factors and management of patients with clinically localized melanoma, in particular among the aforementioned special populations. Show less
In a social environment composed mostly of people with typical hearing, deaf or hard of hearing (DHH) children experience social interactions differently from their typically hearing (TH) peers,... Show moreIn a social environment composed mostly of people with typical hearing, deaf or hard of hearing (DHH) children experience social interactions differently from their typically hearing (TH) peers, which could guide them towards different patterns for processing other people’s emotions. This thesis aimed to unravel whether hearing status affects how children encode, interpret, and react to others’ emotions in a social context, and whether their responses are associated with psychosocial functioning, using a variety of measures that included eye tracking, pupillometry, behavioral tasks, parent reports, and longitudinal follow-up. DHH children’s skills for perceiving others’ basic emotions were on par with their TH peers. Improved emotional functioning was associated with improved psychosocial functioning to a similar degree in DHH and TH children alike. Yet, DHH children still faced difficulties when they had to process an emotion with adequate knowledge about social rules and causes of emotions. Moreover, DHH children used a visual cue-based encoding strategy to compensate for ambiguous or unavailable information in social situations, and recruited more cognitive resources to process unfamiliar emotional expressions. The findings underscore the need to look into possible qualitative differences between typical and atypical development. These individual differences reflect compensatory strategies to support daily living, or signal a need for support in a certain domain. Show less
In coeliac disease effective long-term management and screening programs are lacking for children as well as for adults. In this thesis we tried to contribute to this close this gap. We showed that... Show moreIn coeliac disease effective long-term management and screening programs are lacking for children as well as for adults. In this thesis we tried to contribute to this close this gap. We showed that nutritional deficiencies present at diagnosis recover within 1 year of gluten-free diet and demonstrated that standard blood investigations besides coeliac specific serology are not necessary after 1 year of follow-up. Furthermore, the short dietary questionnaire developed by Biagi does not provide more information on diet adherence than coeliac specific antibodies, whereas a standardized dietary interview does. In the domain of screening, we demonstrated that parents from coeliac families support HLA-typing in their children in order to assess risk for the disease. Detailed information should be offered to them in order to prevent misinterpretation of the results, Antibody-testing should be offered to all HLA-DQ2 and/or DQ8 positive pediatric first degree relatives, with regular intervals until the age of 10. With regard to screening in asymptomatic diabetic children, normal duodenal mucosa is present in 12% of the children when biopsied in case of a TG2A titer of > 3xULN. Follow-up serology seems safe and appropriate in such cases. Show less
Childhood obesity is an increasing health issue. In the first part of this thesis comorbidities in children with obesity were studied, concerning the diagnostic process and dosing regimens. In... Show moreChildhood obesity is an increasing health issue. In the first part of this thesis comorbidities in children with obesity were studied, concerning the diagnostic process and dosing regimens. In children with obesity and respiratory symptoms the diagnosis of asthma was studied and in children with ADHD dosing regimens. Overtreatment as a consequence of overdiagnosis was frequently observed in children with obesity and asthma and undertreatment due to relative underdosing in the ADHD population with obesity. This highlights the necessity for accurate diagnostic processes alongside dosing regimens based on pharmacokinetic changes caused by obesity. The focus in the second part of this thesis was on screening for complications of obesity namely insulin resistance and cardiovascular diseases. Given the high prevalence of insulin resistance and the observed changes of cardiovascular parameters, screening on cardiometabolic complications is warranted in all children with obesity. Pharmacological treatment with metformin in addition to lifestyle intervention was studied in the last part of this thesis. Given the favorable effect on BMI in children and adults and the maintenance of weight loss and reduction in progression towards T2DM in adults, metformin can be considered in children with obesity and insulin resistance in addition to lifestyle intervention. Show less
De overheid mag kinderen onder voorwaarden van hun vrijheid beroven met als doel ze op te voeden en te beschermen. In de Nederlandse context wordt deze vorm van vrijheidsberoving ‘gesloten... Show moreDe overheid mag kinderen onder voorwaarden van hun vrijheid beroven met als doel ze op te voeden en te beschermen. In de Nederlandse context wordt deze vorm van vrijheidsberoving ‘gesloten jeugdhulp’ genoemd, geregeld in de Jeugdwet. Met dit onderzoek is beoogd om een kinder- en mensenrechtentoetsingskader op te stellen, waaraan de Nederlandse wet en de toepassing getoetst wordt. Tevens biedt het onderzoek inzicht in 200 jaar historie.Verder zijn 586 rechterlijke uitspraken over een periode van 10 jaar (2008-2017) geanalyseerd. Hieruit blijkt dat een plaatsing vaak gebaseerd is op het inzetten van acute hulp in een situatie waar in niets anders mogelijk lijkt te zijn. Doorgaans wordt daarbij onvoldoende gekeken naar het doel van deze plaatsing en de vrijheidsbeperkingen die dit met zich meebrengt.In dit onderzoek komen ten slotte 23 kinderen aan het woord die te maken kregen met een gesloten uithuisplaatsing. Uit het onderzoek blijkt dat de legitimiteit van het op grote schaal toepassen van deze maatregel onder druk staat, met name omdat het nogal eens ontbreekt aan passende zorg. Verschillende aanbevelingen worden gedaan om de legitimiteit te verbeteren, onder meer door middel van verdieping van het juridische toetsingskader, verkorting van de maximale duur van een plaatsing. Show less
International Commercial Surrogacy (ICS) has emerged over the past decade as a modern method of family formation. ICS is unregulated internationally and domestic laws are struggling to keep pace... Show moreInternational Commercial Surrogacy (ICS) has emerged over the past decade as a modern method of family formation. ICS is unregulated internationally and domestic laws are struggling to keep pace with ICS. However, a child is at the centre of every ICS arrangement, and children conceived and born through ICS are at a heightened risk of their rights being infringed.Written over the course of time when ICS has rapidly developed, this book explores why and how the child's rights are at risk in ICS, and seeks to apply the standards and norms of the United Nations Convention on the Rights of the Child to the ICS context. This book proposes approaches for balancing the competing rights and interests of the child and other parties in ICS. It presents a framework for protecting the rights of children born through ICS, illustrating that this is achievable in practice, in the absence of international consensus on ICS as a phenomenon.This book is relevant for child rights practitioners and academics, and useful for policy-makers, legislators and national and international decision-makers grappling with the children’s and human rights issues presented by this 21st century human rights challenge. Show less
We studied a novel triage approach to the organisation of routine assessments by Preventive Child Health care (PCH), including task-shifting among professionals. In the triage approach, access to... Show moreWe studied a novel triage approach to the organisation of routine assessments by Preventive Child Health care (PCH), including task-shifting among professionals. In the triage approach, access to PCH, and the detection of the health problems studied, were comparable with the usual approach. The efficient deployment of PCH professionals using triage and task-shifting reduced the costs and involvement of PCH physicians and nurses in routine assessments, particularly in the youngest age group (5 to 6 years). The associated release of workforce and budgets may create more opportunities for the delivery of care to children and their families with specific health-care needs. In our study, in the triage approach PCH physicians and nurses provided more demand-driven care at the request of parents and others such as school professionals. We have emphasised the importance of making the PCH programme more flexible to create time for PCH professionals to collaborate with professionals from the school system, and from the youth care and primary care systems, with the aim of improving joint commitment to early detection, and the delivery of more coordinated care. More research is needed into the outcomes of referral to extra care and into the cost benefits of the triage approach. Show less
The aim of this thesis was to study the link between hearing loss, language skills, and social functioning in deaf and hard of hearing (DHH) children. Sufficient language skills are an... Show moreThe aim of this thesis was to study the link between hearing loss, language skills, and social functioning in deaf and hard of hearing (DHH) children. Sufficient language skills are an essential prerequisite to develop appropriate communication skills, in order to join in conversations with others. Both their hearing loss and their diminished communication skills prevent DHH children from learning by observing their surroundings (incidental learning). As a result, DHH children showed more difficulty in understanding others’ thoughts and wishes (Theory of Mind or ToM). DHH teenagers reported to have difficulties with understanding others’ emotions and showed lower levels of prosocial behavior. Higher communication skills, but not language skills, were related to better ToM development and higher empathic abilities. Second, the role of early identification and intervention of hearing loss on the social-emotional development of DHH children was studied. This was illustrated in a longitudinal study showing that early cochlear implantation resulted in higher language and communication skills. In turn, these improved skills prevented the development of early signs of psychopathology. To conclude, this thesis shows that in order to stimulate the social-emotional development of DHH children, their opportunities for incidental learning have to be increased. Show less
In haar proefschrift heeft Katinka Beker onderzoek gedaan naar de fundamentele leesprocessen die ten grondslag liggen aan leren van (meerdere) teksten. Uit een combinatie van literatuur- en... Show moreIn haar proefschrift heeft Katinka Beker onderzoek gedaan naar de fundamentele leesprocessen die ten grondslag liggen aan leren van (meerdere) teksten. Uit een combinatie van literatuur- en experimenteel onderzoek is gebleken dat het activeren van eerder gelezen informatie en achtergrondkennis tijdens het lezen belangrijk is bij het leren van teksten. Door een nieuw onderzoeksparadigma te gebruiken kon op een subtiele manier onderzocht worden of informatie uit eerder gelezen teksten of achtergrondkennis actief was tijdens het lezen van nieuwe teksten. Het paradigma kan in toekomstig onderzoek gebruikt worden om te onderzoeken onder welke omstandigheden informatie uit eerder gelezen teksten of achtergrondkennis geactiveerd wordt tijdens het lezen van nieuwe teksten. Het onderzoek is vooral fundamenteel van aard, maar bevat ook een aantal aanknopingspunten waarmee in toekomstig praktijkgericht onderzoek mogelijk een vertaalslag gemaakt kan worden voor de onderwijspraktijk. Zo lijken consolidatie- en verrijkingsprocessen belangrijk te zijn bij het leren van teksten. Show less
Prevalence of childhood obesity is increasing. Insulin resistance is a consequence of childhood obesity, and it has a keyrole in the development of cardiometabolic complications, such as... Show more Prevalence of childhood obesity is increasing. Insulin resistance is a consequence of childhood obesity, and it has a keyrole in the development of cardiometabolic complications, such as diabetes mellitus. In the first part of this thesis, the epidemiology of insulin resistance has been described. Since there is no clear definition for insulin resistance, the prevalence of IR remains unclear. In addition, the use of IR in the screening for diabetes mellitus in obese children was evaluated. In the second part of the thesis, treatment of obese children with insulin resistance is discussed. In a randomized controlled trial of 18 months, children were treated with either metformin or placebo in addition to lifestyle intervention. Body mass index in children treated with metformin remained stable during the 18 months, whereas placebo-treated children had an increase in body mass index. Finally, the treatment with metformin under the strict circumstances of the clinical trial was compared to treatment with metformin in daily practice during 18 months. Both groups showed similar results regarding body mass index during metformin treatment. Show less
Coeliac disease (CD) is an immune-mediated systemic disorder elicited by gluten in genetically susceptible individuals. The aim of this thesis was to investigate the influence of infant feeding on... Show moreCoeliac disease (CD) is an immune-mediated systemic disorder elicited by gluten in genetically susceptible individuals. The aim of this thesis was to investigate the influence of infant feeding on prevention and development of childhood CD (part 1) and to explore new strategies for improvement of care for CD children and young adults (part 2). In part 1, the European multi-centre randomized double-blind placebo-controlled dietary intervention-study in high-risk children (www.preventcd.com) is presented. Based on retrospective studies suggesting a ‘window of opportunity’ for primary prevention of CD, parents were advised to introduce gluten between 4–6 months of age. Our results show that this did not reduce the risk of CD by 3 years of age and contributed to a new European guideline stating that gluten may be introduced between age 4-12 months. Part 2 shows that physicians overestimate the CD specific health-related quality-of-life (HRQOL) of CD patients, supporting implementation of self-reported CD-specific HRQOL measurements during follow-up. Compared to traditional hospital visits for treated CD, E-health was cost-saving, satisfactory, and significantly improved the CD-specific HRQOL. As E-health requires a point-of-care test suitable for follow-up of treated CD, three different tests were compared with conventional ELISA and one was found to be suitable. Show less
Increasingly, pleas are made for extending the involvement of minors in decision-making about participation in pediatric research. However, a number of issues arise from this desired... Show more Increasingly, pleas are made for extending the involvement of minors in decision-making about participation in pediatric research. However, a number of issues arise from this desired participation of minors. First, involvement in decision-making requires children and adolescents to be adequately informed about what participation in research entails. Second, the plea for increased involvement in decision-making requires further investigation whether children indeed can, should and want to play a role in the decision about research participation. This thesis addresses these issues and thereby contributes to insights in how to empower minors in the context of informed consent for research participation. New informed consent material was developed in close cooperation with children and other end-users, the process of which is described and evaluated. Also, insights in the role that minors can, should and want to play in the informed consent procedure are described. These insights were obtained by reviewing multidisciplinary scientific evidence on the competence of minors, by an ethical reflection on the view on children that we should adopt, and by consulting minors themselves about the perspectives on their role in decision-making. Finally, based on this research, recommendations are provided on how to empower minors in decision-making about research participation. Show less
When trying to understand texts, readers engage in various cognitive processes. If all goes well, the engagement in these cognitive processes during reading results in the construction of a... Show moreWhen trying to understand texts, readers engage in various cognitive processes. If all goes well, the engagement in these cognitive processes during reading results in the construction of a coherent mental representation of the text, the essence of successful reading comprehension. To construct such a representation, readers need to monitor the coherence of the text and of their emerging mental representation of what the text is about. The central aim of the empirical studies described is to examine coherence-monitoring processes across development by measuring reader’s ability to detect coherence breaks during reading of narratives. The first part of this dissertation consists of three empirical studies (chapter 2-4). The first study examined whether good and poor comprehenders at age 8-9 and 10-11 detected coherence-breaks during and/or after reading. The second study builds on the first study by examining the protracted development of coherence monitoring in an adolescent population (ages 10-22) using the same task under more challenging circumstances. The third study explored the neural correlates of coherence-break detection in young adults in an fMRI study. The second part of this dissertation consists of two conceptual chapters in which the results are summarized and discussed in a broader theoretical perspective (chapter 5-6). Show less
Special populations are groups of patients that may respond differently to drug treatment due to a variety of factors, such as age or disease. Therefore, in drug development dedicated clinical... Show moreSpecial populations are groups of patients that may respond differently to drug treatment due to a variety of factors, such as age or disease. Therefore, in drug development dedicated clinical studies are often required to determine the optimal dose for these (vulnerable) patient groups. Such studies are complicated by ethical and practical barriers that can hinder the objective of the study when not well designed. To optimise the design of such studies, the application of model-based approaches is essential. In this thesis, we aimed to develop a semi-physiological framework that constitutes a scientific basis for optimisation of study designs in special populations. First, we examined the accuracy of existing approaches in paediatric patients. For the "allometric scaling plus maturation function" approach, the accuracy was shown low especially in young children. An alternative approach was found in the physiological well-stirred-model of hepatic clearance. On this basis, the semi-physiological PK models were developed by interfacing descriptive compartmental pharmacokinetic models with the well-stirred-model of hepatic clearance, and a mechanistic description of plasma-protein binding. The performance of these models was evaluated using two paradigm-drugs (solifenacin and tamsulosin) and was shown successful for the prediction of the pharmacokinetics in paediatric, hepatic-impaired and renal-impaired patients. Show less
This thesis describes the potential role of non-invasive measurement of pharmacokinetics (pk) and pharmacodynamics (pd) in the research and development of central nervous system (cns) stimulants or... Show moreThis thesis describes the potential role of non-invasive measurement of pharmacokinetics (pk) and pharmacodynamics (pd) in the research and development of central nervous system (cns) stimulants or depressants for children and adolescents. First, we evaluated the feasibility of using saliva as an alternative to plasma in two studies on psychostimulants (caffeine and methylphenidate). Second, neuropsychological and neurophysiological functions were measured longitudinally using the NeuroCart, a battery of tests developed at the Centre for Human Drug Research (chdr, Leiden, The Netherlands) that includes non-invasive tests for alertness, visuomotor coordination, motor control, memory, and subjective drug effects. Using a non-invasive approach, age-dependent differences in alcohol pk and pd were evaluated between healthy adolescents and adults. This thesis concludes with the report of two clinical trials that were designed to evaluate age-appropriate formulations of sedative drugs that have the potential for use in children. Show less
Large numbers of children all over the world face significant health risks, such as infectious and chronic diseases, malnutrition, injuries and the consequences of natural disasters, protracted... Show moreLarge numbers of children all over the world face significant health risks, such as infectious and chronic diseases, malnutrition, injuries and the consequences of natural disasters, protracted armed conflicts and poverty. Every year, 4 million babies die within the first month of their life and almost 8 million children under the age of five die from preventable diseases such as malaria, pneumonia, measles and diarrhoea. These general statistics do not reveal the underlying inequalities in health between and within countries. One of the causes of the inequalities is that, in many countries, vulnerable groups of children have no or only limited access to health services. This research aims to identify the standards in international law for realizing the right to the highest attainable standard of health of the child. The central questions that are analysed: a. What priorities derive from the concept of the highest attainable standard of health of the child, its definition and the interpretation of the key constituent elements on the basis of international human rights law? b. How should this concept be implemented in the light of the international human rights standards? Show less
