• CA19-9 and Apolipoprotein-A2 isoforms as detection markers for pancreatic cancer - a prospective evaluation.

      Honda, K; Katzke, V A; Hüsing, A; Okaya, S; Shoji, H; Onidani, K; Olsen, A; Tjønneland, A; Overvad, K; Weiderpass, E; Vineis, P; Muller, D; Tsilidis, K K; Palli, D; Pala, V; Tumino, R; Naccarati, A; Panico, S; Aleksandrova, K; Boeing, H; Bueno-de-Mesquita, H B; Peeters, P H; Trichopoulou, A; Lagiou, P; Khaw, K-T; Wareham, N J; Travis, R C; Merino, S; Duell, E J; Rodríguez-Barranco, M; Chirlaque, M D; Barricarte, A; Rebours, V; Boutron-Ruault, M-C; Romana Mancini, F; Brennan, P; Scelo, G; Manjer, J; Sund, M; Öhlund, D; Canzian, F; Kaaks, R (2018-09-27)
      Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. This study provides a first prospective evaluation of an ApoA2 isoform ("ApoA2-ATQ/AT"), alone and in combination with carbohydrate antigen 19-9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6-18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6-18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6-18 or ≤18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging. This article is protected by copyright. All rights reserved.
    • Can universal access be achieved in a voluntary private health insurance market? Dutch private insurers caught between competing logics.

      Vonk, Robert A A; Schut, Frederik T (2018-05-07)
      For almost a century, the Netherlands was marked by a large market for voluntary private health insurance alongside state-regulated social health insurance. Throughout this period, private health insurers tried to safeguard their position within an expanding welfare state. From an institutional logics perspective, we analyze how private health insurers tried to reconcile the tension between a competitive insurance market pressuring for selective underwriting and actuarially fair premiums (the insurance logic), and an upcoming welfare state pressuring for universal access and socially fair premiums (the welfare state logic). Based on primary sources and the extant historiography, we distinguish six periods in which the balance between both logics changed significantly. We identify various strategies employed by private insurers to reconcile the competing logics. Some of these were temporarily successful, but required measures that were incompatible with the idea of free entrepreneurship and consumer choice. We conclude that universal access can only be achieved in a competitive individual private health insurance market if this market is effectively regulated and mandatory cross-subsidies are effectively enforced. The Dutch case demonstrates that achieving universal access in a competitive private health insurance market is institutionally complex and requires broad political and societal support.
    • Can we predict tuberculosis cure? What tools are available?

      Goletti, Delia; Lindestam Arlehamn, Cecilia S; Scriba, Thomas J; Anthony, Richard; Cirillo, Daniela Maria; Alonzi, Tonino; Denkinger, Claudia M; Cobelens, Frank (2018-11)
      Antibiotic treatment of tuberculosis takes ≥6 months, putting a major burden on patients and health systems in large parts of the world. Treatment beyond 2 months is needed to prevent tuberculosis relapse by clearing remaining, drug-tolerant Mycobacterium tuberculosis bacilli. However, the majority of patients treated for only 2-3 months will cure without relapse and do not need prolonged treatment. Assays that can identify these patients at an early stage of treatment may significantly help reduce the treatment burden, while a test to identify those patients who will fail treatment may help target host-directed therapies.In this review we summarise the state of the art with regard to discovery of biomarkers that predict relapse-free cure for pulmonary tuberculosis. Positron emission tomography/computed tomography scanning to measure pulmonary inflammation enhances our understanding of "cure". Several microbiological and immunological markers seem promising; however, they still need a formal validation. In parallel, new research strategies are needed to generate reliable tests.
    • Carbapenemase-producerende enterobacteriën in Nederland : Onopgemerkte versprewiding naar verschillende regio's.

      Leenstra, T; Bosch, T; Vlek, A L; Bonten, M J M; van der Lubben, I M; de Greeff, S C (2017-10-24)
      - Carbapenemase producing Enterobacteriaceae (CPE), including Klebsiella pneumoniae and Escherichia coli, are only sporadically seen in the Netherlands and then mainly in patients who have been transferred from foreign hospitals.- CPE are resistant to virtually all beta-lactam antibiotics, including carbapenems, e.g., meropenem and imipenem. Several genes, e.g., OXA-48, KPC and NDM-1, code for carbapenemase enzymes that deactivate carbapenems.- Control of CPE focuses on timely identification of patients who are infected or are carriers and the application of preventive measures to prevent spread.- Genotypic analysis of CPE isolates submitted to the national CPE surveillance revealed close relationships between 8 NDM-1 positive K. pneumoniae isolates of patients from different parts of the Netherlands and isolates obtained through contact tracing during a known hospital outbreak.- Based on retrospective epidemiological investigation, no shared exposure could be found.- These findings indicate unnoticed spread of CPE in the Netherlands.
    • Cardiovascular risk model performance in women with and without hypertensive disorders of pregnancy.

      Dam, Veerle; Onland-Moret, N Charlotte; Verschuren, W M Monique; Boer, Jolanda M A; Benschop, Laura; Franx, Arie; Moons, Karel G M; Boersma, Eric; van der Schouw, Yvonne T (2018-09-12)
      Compare the predictive performance of Framingham Risk Score (FRS), Pooled Cohort Equations (PCEs) and Systematic COronary Risk Evaluation (SCORE) model between women with and without a history of hypertensive disorders of pregnancy (hHDP) and determine the effects of recalibration and refitting on predictive performance.
    • Cascading effects of predator activity on tick-borne disease risk.

      Hofmeester, Tim R; Jansen, Patrick A; Wijnen, Hendrikus J; Coipan, Elena C; Fonville, Manoj; Prins, Herbert H T; Sprong, Hein; van Wieren, Sipke E (2017-07-26)
      Predators and competitors of vertebrates can in theory reduce the density of infected nymphs (DIN)-an often-used measure of tick-borne disease risk-by lowering the density of reservoir-competent hosts and/or the tick burden on reservoir-competent hosts. We investigated this possible indirect effect of predators by comparing data from 20 forest plots across the Netherlands that varied in predator abundance. In each plot, we measured the density of questing Ixodes ricinus nymphs (DON), DIN for three pathogens, rodent density, the tick burden on rodents and the activity of mammalian predators. We analysed whether rodent density and tick burden on rodents were correlated with predator activity, and how rodent density and tick burden predicted DON and DIN for the three pathogens. We found that larval burden on two rodent species decreased with activity of two predator species, while DON and DIN for all three pathogens increased with larval burden on rodents, as predicted. Path analyses supported an indirect negative correlation of activity of both predator species with DON and DIN. Our results suggest that predators can indeed lower the number of ticks feeding on reservoir-competent hosts, which implies that changes in predator abundance may have cascading effects on tick-borne disease risk.
    • Case of seasonal reassortant A(H1N2) influenza virus infection, the Netherlands, March 2018.

      Meijer, Adam; Swaan, Corien M; Voerknecht, Martin; Jusic, Edin; van den Brink, Sharon; Wijsman, Lisa A; Voordouw, Bettie Cg; Donker, Gé A; Sleven, Jacqueline; Dorigo-Zetsma, Wendelien W; Svraka, Sanela; van Boven, Michiel; Haverkate, Manon R; Timen, Aura; van Dissel, Jaap T; Koopmans, Marion Pg; Bestebroer, Theo M; Fouchier, Ron Am (2018-04)
      A seasonal reassortant A(H1N2) influenza virus harbouring genome segments from seasonal influenza viruses A(H1N1)pdm09 (HA and NS) and A(H3N2) (PB2, PB1, PA, NP, NA and M) was identified in March 2018 in a 19-months-old patient with influenza-like illness (ILI) who presented to a general practitioner participating in the routine sentinel surveillance of ILI in the Netherlands. The patient recovered fully. Further epidemiological and virological investigation did not reveal additional cases.
    • CDHR3 gene variation and childhood bronchiolitis.

      Husby, Anders; Pasanen, Anu; Waage, Johannes; Sevelsted, Astrid; Hodemaekers, Hennie; Janssen, Riny; Karjalainen, Minna K; Stokholm, Jakob; Chawes, Bo L; Korppi, Matti; Wennergren, Göran; Heinzmann, Andrea; Bont, Louis; Bisgaard, Hans; Bønnelykke, Klaus (2017-11)
    • Challenges in characterizing the environmental fate and effects of carbon nanotubes and inorganic nanomaterials in aquatic systems

      Laux, Peter; Riebeling, Christian; Booth, Andy M.; Brain, Joseph D.; Brunner, Josephine; Cerrillo, Cristina; Creutzenberg, Otto; Estrela-Lopis, Irina; Gebel, Thomas; Johanson, Gunnar; Jungnickel, Harald; Kock, Heiko; Tentschert, Jutta; Tlili, Ahmed; Schäffer, Andreas; Sips, Adriënne J. A. M.; Yokel, Robert A.; Luch, Andreas; Department of Chemical and Product Safety; Department of Chemical and Product Safety; SINTEF Ocean; Harvard T. H. Chan School of Public Health; Department of Chemical and Product Safety; IK4-Tekniker; Department of Inhalation Toxicology; Institute of Medical Physics & Biophysics; German Federal Institute for Occupational Safety and Health (BAuA); Institute of Environmental Medicine; Department of Chemical and Product Safety; Department of Inhalation Toxicology; Department of Chemical and Product Safety; Department of Environmental Toxicology; Institute for Environmental Research; National Institute for Public Health & the Environment (RIVM); Pharmaceutical Sciences; Department of Chemical and Product Safety (2018)
      Characterization of carbon nanotube dispersions requires measurement of both, concentration and surface area.
    • Changes in (risk) behavior and HPV knowledge among Dutch girls eligible for HPV vaccination: an observational cohort study.

      Donken, Robine; Tami, Adriana; Knol, Mirjam J; Lubbers, Karin; van der Sande, Marianne A B; Nijman, Hans W; Daemen, Toos; Weijmar Schultz, Willibrord C M; de Melker, Hester E (2018-07-05)
      Implementation of human papillomavirus (HPV) vaccination raised concerns that vaccination could lead to riskier sexual behavior. This study explored how possible differences in sexual behavior and HPV knowledge developed over time between HPV-vaccinated and unvaccinated girls.
    • Changes in Emissions of Ozone-Depleting Substances from China Due to Implementation of the Montreal Protocol.

      Fang, Xuekun; Ravishankara, A R; Velders, Guus J M; Molina, Mario J; Su, Shenshen; Zhang, Jianbo; Hu, Jianxin; Prinn, Ronald G (2018-10-02)
      The ozone layer depletion and its recovery, as well as the climate influence of ozone-depleting substances (ODSs) and their substitutes that influence climate, are of interest to both the scientific community and the public. Here we report on the emissions of ODSs and their substitute from China, which is currently the largest consumer (and emitter) of these substances. We provide, for the first time, comprehensive information on ODSs and replacement hydrofluorocarbon (HFC) emissions in China starting from 1980 based on reported production and usage. We also assess the impacts (and costs) of controls on ODS consumption and emissions on the ozone layer (in terms of CFC-11-equivalent) and climate (in CO2-equivalent). In addition, we show that while China's future ODS emissions are likely to be defined as long as there is full compliance with the Montreal Protocol; its HFC emissions through 2050 are very uncertain. Our findings imply that HFC controls over the next decades that are more stringent than those under the Kigali Amendment to the Montreal Protocol would be beneficial in mitigating global climate change.
    • Changes in LXR signaling influence early-pregnancy lipogenesis and protect against dysregulated fetoplacental lipid homeostasis.

      Nikolova, Vanya; Papacleovoulou, Georgia; Bellafante, Elena; Borges Manna, Luiza; Jansen, Eugene; Baron, Silvère; Abu-Hayyeh, Shadi; Parker, Malcolm; Williamson, Catherine (2017-10-01)
      Human pregnancy is associated with enhanced de novo lipogenesis in the early stages followed by hyperlipidemia during advanced gestation. Liver X receptors (LXRs) are oxysterol-activated nuclear receptors that stimulate de novo lipogenesis and also promote the efflux of cholesterol from extrahepatic tissues followed by its transport back to the liver for biliary excretion. Although LXR is recognized as a master regulator of triglyceride and cholesterol homeostasis, it is unknown whether it facilitates the gestational adaptations in lipid metabolism. To address this question, biochemical profiling, protein quantification, and gene expression studies were used, and gestational metabolic changes in T0901317-treated wild-type mice and Lxrab-/- mutants were investigated. Here, we show that altered LXR signaling contributes to the enhanced lipogenesis in early pregnancy by increasing the expression of hepatic Fas and stearoyl-CoA desaturase 1 (Scd1). Both the pharmacological activation of LXR with T0901317 and the genetic ablation of its two isoforms disrupted the increase in hepatic fatty acid biosynthesis and the development of hypertriglyceridemia during early gestation. We also demonstrate that absence of LXR enhances maternal white adipose tissue lipolysis, causing abnormal accumulation of triglycerides, cholesterol, and free fatty acids in the fetal liver. Together, these data identify LXR as an important factor in early-pregnancy lipogenesis that is also necessary to protect against abnormalities in fetoplacental lipid homeostasis.
    • Characterisation of the natural environment: quantitative indicators across Europe.

      Smith, Graham; Cirach, Marta; Swart, Wim; Dėdelė, Audrius; Gidlow, Christopher; van Kempen, Elise; Kruize, Hanneke; Gražulevičienė, Regina; Nieuwenhuijsen, Mark J (2017-04-26)
      The World Health Organization recognises the importance of natural environments for human health. Evidence for natural environment-health associations comes largely from single countries or regions, with varied approaches to measuring natural environment exposure. We present a standardised approach to measuring neighbourhood natural environment exposure in cities in different regions of Europe.
    • Characterization of Enterococcus Isolates Colonizing the Intestinal Tract of Intensive Care Unit Patients Receiving Selective Digestive Decontamination

      Bello Gonzalez, Teresita d. J.; Pham, Phu; Top, Janetta; Willems, Rob J. L.; van Schaik, Willem; van Passel, Mark W. J.; Smidt, Hauke (2017-08-28)
    • Characterizing Adult Sleep Behavior Over 20 Years-The Population-Based Doetinchem Cohort Study.

      Zomers, Margot L; Hulsegge, Gerben; van Oostrom, Sandra H; Proper, Karin I; Verschuren, W M Monique; Picavet, H Susan J (2017-07-01)
      To describe sleep duration patterns of adults over a 20-year period; to compare sociodemographic, lifestyle, and health characteristics across these patterns; and to relate the patterns to sleep quality.
    • Chemical composition and source identification of PM 10 in five North Western European cities

      Hama, Sarkawt M.L.; Cordell, Rebecca L.; Staelens, Jeroen; Mooibroek, Dennis; Monks, Paul S. (2018-12)
    • Chikungunya virus outbreak in Sint Maarten: Long-term arthralgia after a 15-month period.

      Peters, C M M; Pijnacker, R; Fanoy, E B; Bouwman, L J T; de Langen, L E; van den Kerkhof, J H T C; Reimerink, J; Pilot, E; Henry, M; Oostburg, V Asin; Braks, M A H (2018-11-19)
      The first chikungunya (CHIK) epidemic in the Americas was reported in December 2013. Chikungunya virus (CHIKV) causes an acute febrile illness and is transmitted to humans by Aedes mosquitoes. Although earlier studies have described long-term clinical manifestations of CHIK patients infected with the East/Central/South African (ECSA) genotype, little is known about persistent manifestations in the Caribbean region, for which the Asian genotype is responsible. The objective of this study was to describe the presence of persisting clinical manifestations, specifically arthralgia, in CHIKV-infected patients on the Caribbean Island, Sint Maarten, 15 months after onset of the disease.
    • Childhood infections and common carotid intima media thickness in adolescence.

      Prins-van Ginkel, A C; Bruijning-Verhagen, P C J; Wijga, A H; Bots, M L; Gehring, U; van der Hoek, W; Koppelman, G H; van Rossem, L; Uiterwaal, C S P M; Smit, H A; van der Sande, M A B (2018-11-08)
      Atherosclerotic changes can be measured as changes in common carotid intima media thickness (CIMT). It is hypothesised that repeated infection-associated inflammatory responses in childhood contribute to the atherosclerotic process. We set out to determine whether the frequency of infectious diseases in childhood is associated with CIMT in adolescence. The study is part of the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) population-based birth cohort. At age 16 years, common CIMT was measured. We collected general practitioner (GP) diagnosed infections and prescribed antibiotics. Parent-reported infections were retrieved from annual questionnaires. Linear regression analysis assessed the association between number of infections during the first 4 years of life and common CIMT. Common CIMT measurement, GP and questionnaire data were available for 221 participants. No association was observed between the infection measures and CIMT. In a subgroup analysis, significant positive associations with CIMT were observed in participants with low parental education for 2-3 or ⩾7 GP diagnosed infections (+26.4 µm, 95% CI 0.4-52.4 and +26.8 µm, 95% CI 3.6-49.9, respectively) and ⩾3 antibiotic prescriptions (+35.5 µm, 95%CI 15.8-55.3). Overall, early childhood infections were not associated with common CIMT in adolescence. However, a higher number of childhood infections might contribute to the inflammatory process of atherosclerosis in subgroups with low education, this needs to be confirmed in future studies.
    • Chlamydia psittaci (psittacosis) as a cause of community-acquired pneumonia: a systematic review and meta-analysis.

      Hogerwerf, L; De Gier, B; Baan, B; Van Der Hoek, W (2017)
      Psittacosis is a zoonotic infectious disease caused by the transmission of the bacterium Chlamydia psittaci from birds to humans. Infections in humans mainly present as community-acquired pneumonia (CAP). However, most cases of CAP are treated without diagnostic testing, and the importance of C. psittaci infection as a cause of CAP is therefore unclear. In this meta-analysis of published CAP-aetiological studies, we estimate the proportion of CAP caused by C. psittaci infection. The databases MEDLINE and Embase were systematically searched for relevant studies published from 1986 onwards. Only studies that consisted of 100 patients or more were included. In total, 57 studies were selected for the meta-analysis. C. psittaci was the causative pathogen in 1·03% (95% CI 0·79-1·30) of all CAP cases from the included studies combined, with a range between studies from 0 to 6·7%. For burden of disease estimates, it is a reasonable assumption that 1% of incident cases of CAP are caused by psittacosis.