• Nanomaterial exposures for worker, consumer and the general public

      Kuhlbusch, Thomas A.J.; Wijnhoven, Susan W.P.; Haase, Andrea (2018-04)
    • Nanomaterials Versus Ambient Ultrafine Particles: An Opportunity to Exchange Toxicology Knowledge.

      Stone, Vicki; Miller, Mark R; Clift, Martin J D; Elder, Alison; Mills, Nicholas L; Møller, Peter; Schins, Roel P F; Vogel, Ulla; Kreyling, Wolfgang G; Alstrup Jensen, Keld; et al. (2017)
      A rich body of literature exists that has demonstrated adverse human health effects following exposure to ambient air particulate matter (PM), and there is strong support for an important role of ultrafine (nanosized) particles. At present, relatively few human health or epidemiology data exist for engineered nanomaterials (NMs) despite clear parallels in their physicochemical properties and biological actions inin vitromodels.
    • Nanomedicinal products: a survey on specific toxicity and side effects.

      Brand, Walter; Noorlander, Cornelle W; Giannakou, Christina; De Jong, Wim H; Kooi, Myrna W; Park, Margriet Vdz; Vandebriel, Rob J; Bosselaers, Irene Em; Scholl, Joep Hg; Geertsma, Robert E (2017)
      Due to their specific properties and pharmacokinetics, nanomedicinal products (NMPs) may present different toxicity and side effects compared to non-nanoformulated, conventional medicines. To facilitate the safety assessment of NMPs, we aimed to gain insight into toxic effects specific for NMPs by systematically analyzing the available toxicity data on approved NMPs in the European Union. In addition, by comparing five sets of products with the same active pharmaceutical ingredient (API) in a conventional formulation versus a nanoformulation, we aimed to identify any side effects specific for the nano aspect of NMPs. The objective was to investigate whether specific toxicity could be related to certain structural types of NMPs and whether a nanoformulation of an API altered the nature of side effects of the product in humans compared to a conventional formulation. The survey of toxicity data did not reveal nanospecific toxicity that could be related to certain types of structures of NMPs, other than those reported previously in relation to accumulation of iron nanoparticles (NPs). However, given the limited data for some of the product groups or toxicological end points in the analysis, conclusions with regard to (a lack of) potential nanomedicine-specific effects need to be considered carefully. Results from the comparison of side effects of five sets of drugs (mainly liposomes and/or cytostatics) confirmed the induction of pseudo-allergic responses associated with specific NMPs in the literature, in addition to the side effects common to both nanoformulations and regular formulations, eg, with liposomal doxorubicin, and possibly liposomal daunorubicin. Based on the available data, immunotoxicological effects of certain NMPs cannot be excluded, and we conclude that this end point requires further attention.
    • Nanoparticles induce dermal and intestinal innate immune system responses in zebrafish embryos

      Brun, Nadja R.; Koch, Bjørn E. V.; Varela, Mónica; Peijnenburg, Willie J. G. M.; Spaink, Herman P.; Vijver, Martina G.; Institute of Environmental Sciences (CML); Institute of Biology; Institute of Biology; Institute of Environmental Sciences (CML); et al. (2018)
      Metal and plastic nanoparticles elicit innate immune responses in the skin and intestine of zebrafish embryos potentially serving as key event for AOPs.
    • Narcolepsy and adjuvanted pandemic influenza A (H1N1) 2009 vaccines - Multi-country assessment.

      Weibel, Daniel; Sturkenboom, Miriam; Black, Steven; de Ridder, Maria; Dodd, Caitlin; Bonhoeffer, Jan; Vanrolleghem, Ann; van der Maas, Nicoline; Lammers, Gert Jan; Overeem, Sebastiaan; et al. (2018)
      In 2010, a safety signal was detected for narcolepsy following vaccination with Pandemrix, an AS03-adjuvanted monovalent pandemic H1N1 influenza (pH1N1) vaccine. To further assess a possible association and inform policy on future use of adjuvants, we conducted a multi-country study of narcolepsy and adjuvanted pH1N1 vaccines.
    • A national FFQ for the Netherlands (the FFQ-NL1.0): development and compatibility with existing Dutch FFQs.

      Eussen, Simone Jpm; van Dongen, Martien Cjm; Wijckmans, Nicole Eg; Meijboom, Saskia; Brants, Henny Am; de Vries, Jeanne Hm; Bueno-de-Mesquita, H Bas; Geelen, Anouk; Sluik, Diewertje; Feskens, Edith Jm; et al. (2018-04-22)
      In the Netherlands, various FFQs have been administered in large cohort studies, which hampers comparison and pooling of dietary data. The present study aimed to describe the development of a standardized Dutch FFQ, FFQ-NL1.0, and assess its compatibility with existing Dutch FFQs.
    • National laboratory-based surveillance system for antimicrobial resistance: a successful tool to support the control of antimicrobial resistance in the Netherlands.

      Altorf-van der Kuil, Wieke; Schoffelen, Annelot F; de Greeff, Sabine C; Thijsen, Steven Ft; Alblas, H Jeroen; Notermans, Daan W; Vlek, Anne Lm; van der Sande, Marianne Ab; Leenstra, Tjalling (2017)
      An important cornerstone in the control of antimicrobial resistance (AMR) is a well-designed quantitative system for the surveillance of spread and temporal trends in AMR. Since 2008, the Dutch national AMR surveillance system, based on routine data from medical microbiological laboratories (MMLs), has developed into a successful tool to support the control of AMR in the Netherlands. It provides background information for policy making in public health and healthcare services, supports development of empirical antibiotic therapy guidelines and facilitates in-depth research. In addition, participation of the MMLs in the national AMR surveillance network has contributed to sharing of knowledge and quality improvement. A future improvement will be the implementation of a new semantic standard together with standardised data transfer, which will reduce errors in data handling and enable a more real-time surveillance. Furthermore, the scientific impact and the possibility of detecting outbreaks may be amplified by merging the AMR surveillance database with databases from selected pathogen-based surveillance programmes containing patient data and genotypic typing data.
    • National prevalence estimates of chlamydia and gonorrhoea in the Netherlands.

      Heijne, Janneke C M; van den Broek, Ingrid V F; Bruisten, Sylvia M; van Bergen, Jan E A; de Graaf, Hanneke; van Benthem, Birgit H B (2018-06-20)
      National prevalence estimates of Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhoea) are important for providing insights in the occurrence and control of these STIs. The aim was to obtain national prevalence estimates for chlamydia and gonorrhoea and to investigate risk factors associated with infection.
    • Natural outdoor environments and mental health: Stress as a possible mechanism.

      Triguero-Mas, Margarita; Donaire-Gonzalez, David; Seto, Edmund; Valentín, Antònia; Martínez, David; Smith, Graham; Hurst, Gemma; Carrasco-Turigas, Glòria; Masterson, Daniel; van den Berg, Magdalena; et al. (2017-10)
      Better mental health has been associated with exposure to natural outdoor environments (NOE). However, comprehensive studies including several indicators of exposure and outcomes, potential effect modifiers and mediators are scarce.
    • Necrotising fasciitis as atypical presentation of infection with emerging Neisseria meningitidis serogroup W (MenW) clonal complex 11, the Netherlands, March 2017.

      Russcher, Anne; Fanoy, Ewout; van Olden, Ger D J; Graafland, Antonie D; van der Ende, Arie; Knol, Mirjam J (2017-06-08)
      In March 2017, a patient with necrotising fasciitis caused by Neisseria meningitidis serogroup W (MenW) clonal complex 11 was diagnosed in the Netherlands. Unusual and severe presentations of MenW infections are common in the current European epidemic. In the Netherlands, the incidence of MenW infections increased 10-fold, from an average of 0.03 per 100,000 population in 2002-2014 to 0.29 in 2016. Awareness of atypical presentations enables timely adequate treatment and public health action.
    • Negative Effect of Age, but Not of Latent Cytomegalovirus Infection on the Antibody Response to a Novel Influenza Vaccine Strain in Healthy Adults.

      van den Berg, Sara P H; Wong, Albert; Hendriks, Marion; Jacobi, Ronald H J; van Baarle, Debbie; van Beek, Josine (2018)
      Older adults are more vulnerable to influenza virus infection and at higher risk for severe complications and influenza-related death compared to younger adults. Unfortunately, influenza vaccine responses tend to be impaired in older adults due to aging of the immune system (immunosenescence). Latent infection with cytomegalovirus (CMV) is assumed to enhance age-associated deleterious changes of the immune system. Although lower responses to influenza vaccination were reported in CMV-seropositive compared to CMV-seronegative adults and elderly, beneficial effects of CMV infection were observed as well. The lack of consensus in literature on the effect of latent CMV infection on influenza vaccination may be due to the presence of pre-existing immunity to influenza in these studies influencing the subsequent influenza vaccine response. We had the unique opportunity to evaluate the effect of age and latent CMV infection on the antibody response to the novel influenza H1N1pdm vaccine strain during the pandemic of 2009, thereby reducing the effect of pre-existing immunity on the vaccine-induced antibody response. This analysis was performed in a large study population (n = 263) in adults (18-52 years old). As a control, memory responses to the seasonal vaccination, including the same H1N1pdm and an H3N2 strain, were investigated in the subsequent season 2010-2011. With higher age, we found decreased antibody responses to the pandemic vaccination even within this age range, indicating signs of immunosenescence to this novel antigen in the study population. Using a generalized estimation equation regression model, adjusted for age, sex, and previous influenza vaccinations, we observed that CMV infection in contrast did not influence the influenza virus-specific antibody titer after H1N1pdm vaccination. Yet, we found higher residual protection rates (antibody level ≥40 hemagglutinin units (HAU)) in CMV-seropositive individuals than in CMV-seronegative individuals 6 months and 1 year after pandemic vaccination. In the subsequent season, no effect of age or CMV infection on seasonal influenza vaccine response was observed. In conclusion, we observed no evidence for CMV-induced impairment of antibody responses to a novel influenza strain vaccine in adults. If anything, our data suggest that there might be a beneficial effect of latent CMV infection on the protection rate after novel influenza vaccination.
    • Neglected vector-borne zoonoses in Europe: Into the wild.

      Tomassone, Laura; Berriatua, Eduardo; De Sousa, Rita; Duscher, Gerhard Georg; Mihalca, Andrei Daniel; Silaghi, Cornelia; Sprong, Hein; Zintl, Annetta (2018-02-15)
      Wild vertebrates are involved in the transmission cycles of numerous pathogens. Additionally, they can affect the abundance of arthropod vectors. Urbanization, landscape and climate changes, and the adaptation of vectors and wildlife to human habitats represent complex and evolving scenarios, which affect the interface of vector, wildlife and human populations, frequently with a consequent increase in zoonotic risk. While considerable attention has focused on these interrelations with regard to certain major vector-borne pathogens such as Borrelia burgdorferi s.l. and tick-borne encephalitis virus, information regarding many other zoonotic pathogens is more dispersed. In this review, we discuss the possible role of wildlife in the maintenance and spread of some of these neglected zoonoses in Europe. We present case studies on the role of rodents in the cycles of Bartonella spp., of wild ungulates in the cycle of Babesia spp., and of various wildlife species in the life cycle of Leishmania infantum, Anaplasma phagocytophilum and Rickettsia spp. These examples highlight the usefulness of surveillance strategies focused on neglected zoonotic agents in wildlife as a source of valuable information for health professionals, nature managers and (local) decision-makers. These benefits could be further enhanced by increased collaboration between researchers and stakeholders across Europe and a more harmonised and coordinated approach for data collection.
    • Neighborhood characteristics as determinants of healthcare utilization - a theoretical model.

      Mohnen, Sigrid M; Schneider, Sven; Droomers, Mariël (2019-03-06)
      We propose using neighborhood characteristics as demand-related morbidity adjusters to improve prediction models such as the risk equalization model. Since the neighborhood has no explicit 'place' in healthcare demand models, we have developed the "Neighborhood and healthcare utilization model" to show how neighborhoods matter in healthcare utilization. Neighborhood may affect healthcare utilization via (1) the supply-side, (2) need, and (3) demand for healthcare - irrespective of need. Three pathways are examined in detail to explain how neighborhood characteristics influence healthcare utilization via need: the physiological, psychological and behavioral pathways. We underpin this theoretical model with literature on all relevant neighborhood characteristics relating to health and healthcare utilization. Potential neighborhood characteristics for the risk equalization model include the degree of urbanization, public and open space, resources and facilities, green and blue space, environmental noise, air pollution, social capital, crime and violence, socioeconomic status, stability, and ethnic composition. Air pollution has already been successfully tested as an important predictive variable in a healthcare risk equalization model, and it might be opportune to add more neighborhood characteristics.
    • Neighbourhood green space, social environment and mental health: an examination in four European cities.

      Ruijsbroek, Annemarie; Mohnen, Sigrid M; Droomers, Mariël; Kruize, Hanneke; Gidlow, Christopher; Gražulevičiene, Regina; Andrusaityte, Sandra; Maas, Jolanda; Nieuwenhuijsen, Mark J; Triguero-Mas, Margarita; et al. (2017-07)
      This study examines the relationship between neighbourhood green space, the neighbourhood social environment (social cohesion, neighbourhood attachment, social contacts), and mental health in four European cities.
    • Neighbourhood social and physical environment and general practitioner assessed morbidity.

      Groenewegen, Peter P; Zock, Jan-Paul; Spreeuwenberg, Peter; Helbich, Marco; Hoek, Gerard; Ruijsbroek, Annemarie; Strak, Maciej; Verheij, Robert; Volker, Beate; Waverijn, Geeke; et al. (2018-01)
      The aim of our study was to investigate the association between health enhancing and threatening, and social and physical aspects of the neighbourhood environment and general practitioner (GP) assessed morbidity of the people living there, in order to find out whether the effects of environmental characteristics add up or modify each other. We combined GP electronic health records with environmental data on neighbourhoods in the Netherlands. Cross-classified logistic multilevel models show the importance of taking into account several environmental characteristics and confounders, as social capital effects on the prevalence of morbidity disappear when other area characteristics are taken into account. Stratification by area socio-economic status, shows that the association between environmental characteristics and the prevalence of morbidity is stronger for people living in low SES areas. In low SES areas, green space seems to alleviate effects of air pollution on the prevalence of high blood pressure and diabetes, while the effects of green space and social capital reinforce each other.
    • Neonatal screening parameters in infants with congenital Cytomegalovirus infection.

      Rovito, Roberta; Korndewal, Marjolein J; Schielen, Peter C J I; Kroes, Aloys C M; Vossen, Ann C T M (2017-10)
      Congenital Cytomegalovirus infection (cCMV) is the most common cause of congenital infections worldwide that can cause long-term impairment (LTI). The metabolic alterations due to cCMV are largely unknown. This study aims to assess the metabolites included in the neonatal screening in relation to cCMV and cCMV outcome, allowing the identification of prognostic markers for clinical outcome. Essential amino acids, hormones, carnitines and enzymes from Dried Blood Spots (DBS) were analyzed of 102 children with cCMV and 179 children without cCMV, and they were related to symptoms at birth and LTI at 6years of age. In this cohort, the neonatal screening parameters did not change in relation to cCMV, nor to symptoms at birth or LTI. However, metabolic changes were observed in children born preterm, with lower concentrations of essential amino acids in premature infants with cCMV compared to premature controls. Finally, a higher concentration of palmytoilcarnitine (C16) in the group with higher viral load was observed. Though these data demonstrate limitations in the use of neonatal screening data as predictors for long-term cCMV outcome, the metabolism of preterm neonates with cCMV merits further evaluation.
    • Nested archetypes of vulnerability in African drylands: where lies potential for sustainable agricultural intensification?

      Sietz, D; Ordoñez, J C; Kok, M T J; Janssen, P; Hilderink, H B M; Tittonell, P; Van Dijk, H (2017-09-01)
    • The Netherlands Chlamydia cohort study (NECCST) protocol to assess the risk of late complications following Chlamydia trachomatis infection in women.

      Hoenderboom, B M; van Oeffelen, A A M; van Benthem, B H B; van Bergen, J E A M; Dukers-Muijrers, N H T M; Götz, H M; Hoebe, C J P A; Hogewoning, A A; van der Klis, F R M; van Baarle, D; et al. (2017)
      Chlamydia trachomatis (CT), the most common bacterial sexually transmitted infection (STI) among young women, can result in serious sequelae. Although the course of infection is often asymptomatic, CT may cause pelvic inflammatory disease (PID), leading to severe complications, such as prolonged time to pregnancy, ectopic pregnancy, and tubal factor subfertility. The risk of and risk factors for complications following CT-infection have not been assessed in a long-term prospective cohort study, the preferred design to define infections and complications adequately.
    • Netherlands: The potentials of integrating care via payment reforms

      Struijs, Jeroen N.; Drewes, Hanneke W.; Heijink, Richard; Baan, Caroline A. (2017-06)
      This chapter provides insight in the potential of integrating care through payment reform in the Netherlands. We begin by briefly outlining the main characteristics of the Dutch health care system, which has been transformed into a system of managed competition in the past decade. We focus on health care, because our case study is situated in this setting. We then describe the implementation of the bundled payment for diabetes care as one main example of stimulating nationwide implementation of integrated diabetes care in the Netherlands.