Opportunities for diabetes prevention: risk factors for diabetes and cost-effectiveness of interventions = Mogelijkheden voor diabetespreventie : risicofactoren voor diabetes en kosteneffectiviteit van interventies

Diabetes is already one of the most common chronic diseases in the Dutch population and a substantial further increase in the number of people with diabetes is expected in the near future. A large part of the burden of diabetes can be ascribed to the cardiovascular complications of diabetes which affect quality of life, as well as life expectancy of the patients. In this thesis we explore the opportunities to reduce the future burden of diabetes and cardiovascular diabetes complications in the Dutch population, through prevention. These opportunities depend on the existence of modifiable risk factors for diabetes and the availability of interventions aimed at reducing the incidence of diabetes or diabetes complications. In this thesis we consider the role of weight change, alcohol consumption and smoking as risk factors for diabetes and the cost-effectiveness of preventive interventions in different target populations. Body Mass Index (BMI) is acknowledged as an important modifiable risk factor for diabetes but the role of weight change is not so clear. We showed that, conditional upon initial weight, people who gained weight, had an increased risk of diabetes, compared to persons with relatively stable weight. If adjusted for initial BMI, 5-years weight change was a significant risk factor for diabetes (OR 1.08, 95% CI: 1.04, 1.13 per kg weight change). There was no association between weight change and diabetes incidence, if the association was adjusted for attained BMI (OR 0.99, 95% CI 0.94, 1.04 per kg weight change). We concluded that weight change appears to have no effect on diabetes incidence, beyond its effect on attained BMI. In previous studies, smoking has been reported to increase diabetes risk, while for alcohol consumption the lowest risk for diabetes is generally observed for people who drink moderately. We assessed the associations between these, potentially modifiable, risk factors and diabetes incidence in a Dutch population. We found a u-shaped association between alcohol consumption and diabetes incidence in Dutch women, with the lowest risk for moderate drinkers (1 or 2 drinks per day). We found no evidence for a significant association between alcohol consumption and diabetes incidence in Dutch men. Smoking more than 10 cigarettes per day tended to increase diabetes risk in both men and women, but the associations were not statistically significant. There is substantial evidence that lifestyle interventions focused at improved diet and physical exercise are cost-effective in persons at high risk of developing diabetes. However, the cost-effectiveness of these interventions in other target populations was relatively unknown. We explored the potential long-term health effects and cost-effectiveness of two types of lifestyle interventions: a community-based intervention, targeted at the general Dutch population, and an individual-based intervention, targeted at obese Dutch adults. The long-term effects of these interventions were simulated with a computer-based model: the Chronic Diseases Model (CDM). We showed that the 20-year cumulative incidence of diabetes could be reduced by 0.5-2.4% through large-scale implementation of a community-based intervention, and by 0.4-1.6%, through an individual based intervention for obese adults. Both interventions were projected to reduce lifetime diabetes-related medical costs, but total health care costs increased. The cost-effectiveness ratios ranged from €3,100 to €3,900 per quality adjusted life year (QALY) for the community-based intervention, and from €3,900 to €5,500 per QALY for the individual-based intervention, which means that both interventions are cost-effective according to general standards. We also assessed the potential health effects and cost-effectiveness of seven selected lifestyle interventions for Dutch diabetes patients. Again, long-term effects were simulated with the CDM. There was a large variation in effectiveness between the seven interventions. The reductions in cumulative lifetime incidence of cardiovascular complications among participants ranged from 0.1% to 6.1%. The most effective intervention was a two year structured counseling program, aimed to increase physical activity in inactive diabetes patients. The intervention costs ranged from €124 to €584 per participant, and the cost-effectiveness ratios ranged from €10,000 to €39,000 per QALY. The impact of uncertainty in intervention costs, intervention effects, and long-term maintenance of effects, were quantified with probabilistic sensitivity analyses. These analyses revealed, that four out of seven interventions had a high probability to be very cost-effective. Besides lifestyle, appropriate medication contributes to the prevention of complications in diabetes patients. Guidelines for cardiovascular management recommend lipid lowering treatment for nearly all patients with diabetes. However, in Dutch current practice (in 2007) ‘only’ about 1 out of 3 patients received this treatment. We modeled the long-term effects on cardiovascular complications in the Dutch diabetes population, under the assumption that all patient would use lipid-lowering medication (statins). We showed that treatment for all patients (compared to current care) reduced the life-time cumulative incidence of cardiovascular complications in the Dutch diabetic population by approximately seven percent. With more realistic assumptions about effectiveness and participation, the cumulative incidence of cardiovascular complications decreased by approximately two percent. We conclude that lifestyle interventions can be cost-effective in divers target populations, including diabetes patients. Large-scale implementation of these interventions is justified, and required in order to reduce the future burden of diabetes. However, since the impact on population health, achieved through these interventions, is expected to be moderate, additional research should aim to improve currently available interventions. Simultaneously, opportunities for alternative approaches to the prevention of diabetes and its complications should be further explored

The evaluation of an integrated network approach of preventive care for children with overweight and obesity:Study protocol for an implementation and effectiveness study

Background: Children with overweight often do not receive appropriate integrated care. An innovative integrated network approach of preventive care for overweight children aged 4-12 years old has been developed and implemented in four neighbourhoods of 's-Hertogenbosch, The Netherlands. This new approach focusses on self-management of the family and is based on the principles of stepped and matched care. Youth health care (YHC) nurses support the families in their new role as central care providers. The aim of this study is to evaluate the implementation and effectiveness of this network approach. Methods: The implementation of the new approach (reach, functioning of the central care provider, network functioning and patient satisfaction) is assessed by interviews and checklists with professionals and parents of 4-12 year old overweight or obese children. To evaluate effectiveness, we aim to compare 120 overweight or obese children in 's-Hertogenbosch with 60 overweight or obese children outside 's-Hertogenbosch during one year of YHC involvement. Quality of life, psychosocial problems of the child and parental empowerment are the main outcomes of the effectiveness study. Outcomes are measured with digital questionnaires at inclusion, at three months and one year after inclusion. BMI measurements and referrals are distracted from medical files. Discussion: Integrated care for overweight and obese children is high on the agenda of many municipalities in The Netherlands. The new approach is expected to have beneficial effects for overweight children, their parents and professionals. With the results of this study, we can optimize the support for overweight and obese children and their parents. The first results are expected to be available in 2019

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Autisme.

Begeleiding en behandeling van mensen met autisme vinden voornamelijk plaats in de sectoren Geestelijke Gezondheidszorg, Zorg voor Verstandelijk Gehandicapten, Jeugdhulpverlening en Speciaal Onderwijs. De betrokkenheid van verschillende sectoren binnen de gezondheidszorg en daarbuiten (school, werken en wonen) maakt onderlinge afstemming belangrijk. Betrokken landelijke (koepel)organisaties hebben, in 2000, het ‘Convenant Autisme’ opgesteld, waarin afstemming en integratie binnen de zorgverlening aan de orde komen. Andere landelijke afstemmingsafspraken zijn niet gevonden. Op regionaal niveau zijn er via de literatuur/databanken vijf afstemmingsafspraken achterhaald en 25 via de enquête. Bij de meeste afspraken is de GGZ betrokken, de andere sectoren beduidend minder. In verschillende regio’s zijn intersectorale samenwerkingsverbanden in ontwikkeling. De 25 afspraken hebben voornamelijk betrekking op toegankelijkheid van zorg, zorginhoud, deskundigheidsbevordering bij zorgaanbieders en patiëntgerichtheid. Hiervoor zijn met name gezamenlijke zorgvisies, zorgplannen en protocollen ontwikkeld. Knelpunten in de zorg voor mensen met autisme liggen vooral op het gebied van de toegankelijkheid van zorg (te weinig zorg- en woonaanbod), gebrek aan specifieke deskundigheid bij zorgverleners en gebrek aan afstemming tussen sectoren. Ook is er behoefte aan betere centrale informatievoorziening aan patiënten en ouders

Opportunities for diabetes prevention: risk factors for diabetes and cost-effectiveness of interventions = Mogelijkheden voor diabetespreventie : risicofactoren voor diabetes en kosteneffectiviteit van interventies

Diabetes is already one of the most common chronic diseases in the Dutch population and a substantial further increase in the number of people with diabetes is expected in the near future. A large part of the burden of diabetes can be ascribed to the cardiovascular complications of diabetes which affect quality of life, as well as life expectancy of the patients. In this thesis we explore the opportunities to reduce the future burden of diabetes and cardiovascular diabetes complications in the Dutch population, through prevention. These opportunities depend on the existence of modifiable risk factors for diabetes and the availability of interventions aimed at reducing the incidence of diabetes or diabetes complications. In this thesis we consider the role of weight change, alcohol consumption and smoking as risk factors for diabetes and the cost-effectiveness of preventive interventions in different target populations.Body Mass Index (BMI) is acknowledged as an important modifiable risk factor for diabetes but the role of weight change is not so clear. We showed that, conditional upon initial weight, people who gained weight, had an increased risk of diabetes, compared to persons with relatively stable weight. If adjusted for initial BMI, 5-years weight change was a significant risk factor for diabetes (OR 1.08, 95% CI: 1.04, 1.13 per kg weight change). There was no association between weight change and diabetes incidence, if the association was adjusted for attained BMI (OR 0.99, 95% CI 0.94, 1.04 per kg weight change). We concluded that weight change appears to have no effect on diabetes incidence, beyond its effect on attained BMI.In previous studies, smoking has been reported to increase diabetes risk, while for alcohol consumption the lowest risk for diabetes is generally observed for people who drink moderately. We assessed the associations between these, potentially modifiable, risk factors and diabetes incidence in a Dutch population. We found a u-shaped association between alcohol consumption and diabetes incidence in Dutch women, with the lowest risk for moderate drinkers (1 or 2 drinks per day). We found no evidence for a significant association between alcohol consumption and diabetes incidence in Dutch men. Smoking more than 10 cigarettes per day tended to increase diabetes risk in both men and women, but the associations were not statistically significant.There is substantial evidence that lifestyle interventions focused at improved diet and physical exercise are cost-effective in persons at high risk of developing diabetes. However, the cost-effectiveness of these interventions in other target populations was relatively unknown. We explored the potential long-term health effects and cost-effectiveness of two types of lifestyle interventions: a community-based intervention, targeted at the general Dutch population, and an individual-based intervention, targeted at obese Dutch adults. The long-term effects of these interventions were simulated with a computer-based model: the Chronic Diseases Model (CDM). We showed that the 20-year cumulative incidence of diabetes could be reduced by 0.5-2.4% through large-scale implementation of a community-based intervention, and by 0.4-1.6%, through an individual based intervention for obese adults. Both interventions were projected to reduce lifetime diabetes-related medical costs, but total health care costs increased. The cost-effectiveness ratios ranged from €3,100 to €3,900 per quality adjusted life year (QALY) for the community-based intervention, and from €3,900 to €5,500 per QALY for the individual-based intervention, which means that both interventions are cost-effective according to general standards.We also assessed the potential health effects and cost-effectiveness of seven selected lifestyle interventions for Dutch diabetes patients. Again, long-term effects were simulated with the CDM. There was a large variation in effectiveness between the seven interventions. The reductions in cumulative lifetime incidence of cardiovascular complications among participants ranged from 0.1% to 6.1%. The most effective intervention was a two year structured counseling program, aimed to increase physical activity in inactive diabetes patients. The intervention costs ranged from €124 to €584 per participant, and the cost-effectiveness ratios ranged from €10,000 to €39,000 per QALY. The impact of uncertainty in intervention costs, intervention effects, and long-term maintenance of effects, were quantified with probabilistic sensitivity analyses. These analyses revealed, that four out of seven interventions had a high probability to be very cost-effective.Besides lifestyle, appropriate medication contributes to the prevention of complications in diabetes patients. Guidelines for cardiovascular management recommend lipid lowering treatment for nearly all patients with diabetes. However, in Dutch current practice (in 2007) ‘only’ about 1 out of 3 patients received this treatment. We modeled the long-term effects on cardiovascular complications in the Dutch diabetes population, under the assumption that all patient would use lipid-lowering medication (statins). We showed that treatment for all patients (compared to current care) reduced the life-time cumulative incidence of cardiovascular complications in the Dutch diabetic population by approximately seven percent. With more realistic assumptions about effectiveness and participation, the cumulative incidence of cardiovascular complications decreased by approximately two percent.We conclude that lifestyle interventions can be cost-effective in divers target populations, including diabetes patients. Large-scale implementation of these interventions is justified, and required in order to reduce the future burden of diabetes. However, since the impact on population health, achieved through these interventions, is expected to be moderate, additional research should aim to improve currently available interventions. Simultaneously, opportunities for alternative approaches to the prevention of diabetes and its complications should be further explored

Dorsopathieën.

Negentig procent van de dorsopathieën bestaat uit aspecifieke klachten. Deze worden onderverdeeld in acute, subacute en chronische klachten. Specifieke kwantitatieve gegevens over zorggebruik ontbreken. De huisarts is bij aspecifieke klachten de centrale zorgverlener. De behandeling is activerend en tijdgebonden. Er zijn 4 landelijke afstemmingsafspraken of initiatieven om tot afstemmingsafspraken te komen gevonden. Uit het literatuuronderzoek komen 12 regionale afstemmingsafspraken naar voren, de enquête leverde geen afstemmingsafspraken op. Bij de afstemmingsafspraken zijn voornamelijk psychologen, paramedici en medisch specialisten betrokken. Betrokkenheid van huisartsen en bedrijfsartsen bij afspraken is klein. Afspraken gaan met name over taakverdeling en zorginhoud. Professionele samenwerkingsverbanden als instituten voor rugscholing zijn sterk in opkomst. Knelpunten bij afstemming tussen zorgverleners zijn vooral terug te voeren op het ontbreken van evidence wat betreft diagnostiek en behandeling