• 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; et al. (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.
    • Calculating incidence rates and prevalence proportions: not as simple as it seems.

      Spronk, Inge; Korevaar, Joke C; Poos, René; Davids, Rodrigo; Hilderink, Henk; Schellevis, François G; Verheij, Robert A; Nielen, Mark M J (2019-05-06)
    • Can Menopause Prediction Be Improved With Multiple AMH Measurements? Results From the Prospective Doetinchem Cohort Study.

      de Kat, Annelien C; van der Schouw, Yvonne T; Eijkemans, Marinus J C; Broer, Simone L; Verschuren, W M Monique; Broekmans, Frank J M (2019-11-01)
    • Can Previous Associations of Single Nucleotide Polymorphisms in the , , , and Genes in the Susceptibility to and Severity of Infections Be Confirmed?

      Jukema, Jelmer B; Hoenderboom, Bernice M; van Benthem, Birgit H B; van der Sande, Marianne A B; de Vries, Henry J C; Hoebe, Christian J P A; Dukers-Muijrers, Nicole H T M; Bax, Caroline J; Morré, Servaas A; Ouburg, Sander (2021-01-07)
      Clear inter-individual differences exist in the response to C. trachomatis (CT) infections and reproductive tract complications in women. Host genetic variation like single nucleotide polymorphisms (SNPs) have been associated with differences in response to CT infection, and SNPs might be used as a genetic component in a tubal-pathology predicting algorithm. Our aim was to confirm the role of four genes by investigating proven associated SNPs in the susceptibility and severity of a CT infection. A total of 1201 women from five cohorts were genotyped and analyzed for TLR2 + 2477 G > A, NOD1 + 32656 T -> GG, CXCR5 + 10950 T > C, and IL10 - 1082 A > G. Results confirmed that NOD1 + 32656 T ->GG was associated with an increased risk of a symptomatic CT infection (OR: 1.9, 95%CI: 1.1-3.4, p = 0.02), but we did not observe an association with late complications. IL10 - 1082 A > G appeared to increase the risk of late complications (i.e., ectopic pregnancy/tubal factor infertility) following a CT infection (OR = 2.8, 95%CI: 1.1-7.1, p = 0.02). Other associations were not found. Confirmatory studies are important, and large cohorts are warranted to further investigate SNPs' role in the susceptibility and severity of a CT infection.
    • Can Transgenic Maize Affect Soil Microbial Communities?

      Mulder, Christian; Wouterse, Marja; Raubuch, Markus; Roelofs, Willem; Rutgers, Michiel (2006-09-29)
      The aim of the experiment was to determine if temporal variations of belowground activity reflect the influence of the Cry1Ab protein from transgenic maize on soil bacteria and, hence, on a regulatory change of the microbial community (ability to metabolize sources belonging to different chemical guilds) and/or a change in numerical abundance of their cells. Litter placement is known for its strong influence on the soil decomposer communities. The effects of the addition of crop residues on respiration and catabolic activities of the bacterial community were examined in microcosm experiments. Four cultivars of Zea mays L. of two different isolines (each one including the conventional crop and its Bacillus thuringiensis cultivar) and one control of bulk soil were included in the experimental design. The growth models suggest a dichotomy between soils amended with either conventional or transgenic maize residues. The Cry1Ab protein appeared to influence the composition of the microbial community. The highly enhanced soil respiration observed during the first 72 h after the addition of Bt-maize residues can be interpreted as being related to the presence of the transgenic crop residues. This result was confirmed by agar plate counting, as the averages of the colony-forming units of soils in conventional treatments were about one-third of those treated with transgenic straw. Furthermore, the addition of Bt-maize appeared to induce increased microbial consumption of carbohydrates in BIOLOG EcoPlates. Three weeks after the addition of maize residues to the soils, no differences between the consumption rate of specific chemical guilds by bacteria in soils amended with transgenic maize and bacteria in soils amended with conventional maize were detectable. Reaped crop residues, comparable to post-harvest maize straw (a common practice in current agriculture), rapidly influence the soil bacterial cells at a functional level. Overall, these data support the existence of short Bt-induced ecological shifts in the microbial communities of croplands' soils.
    • 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 assess innovative bio-based chemicals in their early development stage? A comparison between early-stage and life cycle assessments

      Fernandez-Dacosta, C; Wassenaar, PHN; Dencic, I; Zijp, MC; Morao, A; Heugens, EHW; Shen, L (2019-06-11)
    • 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.
    • Capturing multiple-type interactions into practical predictors of type replacement following human papillomavirus vaccination.

      Man, Irene; Auranen, Kari; Wallinga, Jacco; Bogaards, Johannes A (2019-05-27)
      Current HPV vaccines target a subset of the oncogenic human papillomavirus (HPV) types. If HPV types compete during infection, vaccination may trigger replacement by the non-targeted types. Existing approaches to assess the risk of type replacement have focused on detecting competitive interactions between pairs of vaccine and non-vaccine types. However, methods to translate any inferred pairwise interactions into predictors of replacement have been lacking. In this paper, we develop practical predictors of type replacement in a multi-type setting, readily estimable from pre-vaccination longitudinal or cross-sectional prevalence data. The predictors we propose for replacement by individual non-targeted types take the form of weighted cross-hazard ratios of acquisition versus clearance, or aggregate odds ratios of coinfection with the vaccine types. We elucidate how the hazard-based predictors incorporate potentially heterogeneous direct and indirect type interactions by appropriately weighting type-specific hazards and show when they are equivalent to the odds-based predictors. Additionally, pooling type-specific predictors proves to be useful for predicting increase in the overall non-vaccine-type prevalence. Using simulations, we demonstrate good performance of the predictors under different interaction structures. We discuss potential applications and limitations of the proposed methodology in predicting type replacement, as compared to existing approaches. This article is part of the theme issue 'Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses'.
    • 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 Factors Associated With Venous Thromboembolism.

      Gregson, John; Kaptoge, Stephen; Bolton, Thomas; Pennells, Lisa; Willeit, Peter; Burgess, Stephen; Bell, Steven; Sweeting, Michael; Rimm, Eric B; Kabrhel, Christopher; et al. (2019-01-16)
      It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. A panel of several established cardiovascular risk factors.
    • 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.
    • Care Farming for People with Dementia; What Can Healthcare Leaders Learn from This Innovative Care Concept?

      De Bruin, Simone R; Pedersen, Ingeborg; Eriksen, Siren; Hassink, Jan; Vaandrager, Lenneke; Patil, Grete Grindal (2020-01-01)
    • The Care farming sector in the Netherlands: A reflection on its developments and promising innovations.

      Hassink, J; Agricola, H; Veen, EJ; Pijpker, R; de Bruin, SR; van der Meulen, HAB; Plug, LB (2020-06-22)
    • Carry-over of dioxins and PCBs from feed and soil to eggs at low contamination levels-- influence of mycotoxin binders on the carry-over from feed to eggs.

      Hoogenboom, L A P; Kan, C A; Zeilmaker, Marco J; Eijkeren, Jan C H van; Traag, Win A (2006-05-01)
      Laying hens were fed with compound feed containing six different levels of dioxins, dioxin-like PCBs and indicator PCBs for a period of 56 days. This was followed by a period of 56 days on clean feed. Dioxin levels in feed varied from background levels to three times the current EU tolerance limit of 0.75 ng TEQ/kg. At all dose levels a rapid increase was observed in the dioxin levels in eggs. There was a clear linear dose-response relationship between the dioxin levels in eggs and feed. The feed containing 0.4 ng TEQ dioxins per kg resulted in egg levels just above the EU limit of 3 pg TEQ/g fat. Dioxin-like and indicator PCB residues followed a pattern very similar to that of dioxins. Exposure to the highest indicator PCB level of 32 microg/kg resulted in egg levels around 300 ng/g fat. Exposure to dioxins through contaminated soil, mixed at 10% into the feed, resulted in a similar carry-over as from feed. Mycotoxin binders, mixed at 0.5% into the feed, had little effect on the carry-over of dioxins from the feed to the egg. It can be concluded that consumption of feed or soil with even moderate levels of dioxins and dioxin-like PCBs rapidly results in increased levels in eggs. The current EU dioxin limit for feed cannot guarantee egg dioxin levels below the EU-limit.
    • 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; et al. (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.
    • Case study: Enschede fireworks disaster: lessons learned.

      van Kamp, I; van der Velden, P; Yzermans, J (2018-11-01)
    • A case-control study into risk factors for acute hepatitis E in the Netherlands, 2015-2017.

      Tulen, Anna Dolores; Vennema, Harry; van Pelt, Wilfrid; Franz, Eelco; Hofhuis, Agnetha (2019-02-08)
      A case-control study was performed (2015-2017) to identify risk factors for acute hepatitis E in the Netherlands. A questionnaire on potential sources of hepatitis E virus (HEV) exposure, health and socio-demographics was completed by 376 patients with acute hepatitis E, and 1534 controls matched for age, gender and region of residence. Traditional Dutch dry raw sausages of pork muscle meat, called "cervelaat", "snijworst", and "boerenmetworst" were reported by 72% of the patients, and 46% of controls (aOR 3.0; 95%CI 2.2-4.1), with a population attributable fraction (PAF) of 48%. Direct contact with pigs and working with a septic tank were strong risk factors (aOR 3.1; 95%CI 1.3-7.3 and aOR 6.9; 95%CI 1.2-40.8, respectively), with a low PAF (2% and 1%, respectively). Host risk factors were pre-existing liver disease (aOR 3.8; 95%CI 2.0-7.1), diabetes (aOR 2.1; 95%CI 1.4-3.2), immunosuppressive medication (aOR 2.5; 95%CI 1.5-4.1), and gastric acid inhibitors (aOR 2.3; 95%CI 1.7-3.1). Dry raw pork sausages were the major source of HEV infection among our study population. The prevalence and cause of HEV contamination in these pork muscle meat products require further investigation. Infrequently reported, yet strong risk factors were contact with pigs, or a septic tank.