• Radiation Protection for Interventional Fluoroscopy: Results of a Survey Among Dutch Hospitals.

      Bijwaard, Harmen; Valk, Doreth; de Waard-Schalkx, Ischa (2018-06)
      A survey was conducted among 20 Dutch hospitals about radiation protection for interventional fluoroscopy. This was a follow-up of a previous study in 2007 that led to several recommendations for radiation protection for interventional fluoroscopy. The results indicate that most recommendations have been followed. However, radiation-induced complications from interventional procedures are still often not recorded in the appropriate register. Furthermore, even though professionals with appropriate training in radiation protection are usually involved in interventional procedures, this often is not the case when these procedures are carried out outside the radiology department. Although this involvement is not required by Dutch law, it is recommended to have radiation protection professionals present more often at interventional procedures. Further improvements in radiation protection for interventional fluoroscopy may come from a comparison of dose-reducing practices among hospitals, the introduction of diagnostic reference levels for interventional procedures, and a more thorough form of screening and follow-up of patients.

      Smetsers, R C G M; Blaauboer, R O; Dekkers, F; Slaper, H (2018-09-01)
      Radon and thoron progenies in Dutch dwellings cause ~400 cases of lung cancer per year. Some 30% of the risk is due to thoron progeny, which demonstrates that the influence of thoron progeny is much larger than previously anticipated. This was concluded from a national survey in 2500 Dutch dwellings, built since 1930. Radon concentrations (15.6 ± 0.3 Bq m-3 on average) are correlated to type of dwelling, year of construction, ventilation system, location (soil type) and smoking behaviour of inhabitants. The survey data support the establishment of a comparatively low national reference level for radon in dwellings in the Netherlands of 100 Bq m-3, in line with recommendations by WHO and ICRP. Some 24 thousand of the 6.2 million dwellings in the Netherlands (built since 1930) are expected to exceed this level. Around 80% of these are located in the relatively small group of naturally ventilated single-family houses in two designated geographical areas. Radon concentrations above 200 Bq m-3 are rare in the Netherlands and simple and inexpensive measures will be sufficient to reduce enhanced radon concentrations to values below the national reference level. Thoron progeny concentrations (0.64 Bq m-3, on average) show correlations with year of construction and smoking behaviour. In 75 additional dwellings, a pilot study was conducted to determine the relationship between the exhalation of thoron from walls and the concentration of thoron progeny in the room. Thoron exhalation values exceeding the median value of 2.2 × 10-2 Bq m-2 s-1 by a factor 10 or more were found frequently, but enhanced concentrations of thoron progeny were measured only occasionally. Under very unfavourable conditions, however, for instance if phosphogypsum is applied as finishing material on all walls and ceilings in the house, strongly elevated thoron progeny concentrations may occur. This survey yielded a maximum recording of 13.3 Bq m-3. There is no reason to expect that such levels are specific to the Netherlands, indicating that in other regions with low radon levels, thoron may be a more important contributor to the population dose as well.
    • Rapid Assessment of Stakeholder Concerns about Public Health. An Introduction to a Fast and Inexpensive Approach Applied on Health Concerns about Intensive Animal Production Systems.

      Kraaij-Dirkzwager, Marleen; van der Ree, Joost; Lebret, Erik (2017-12-11)
      To effectively manage environmental health risks, stakeholders often need to act collectively. Stakeholders vary in their desire to act due to many factors, such as knowledge, risk perception, interests, and worldviews. Understanding their perceptions of the issues at stake is crucial to support the risk governance process. Even though concern assessment is a pivotal element of risk governance, few tools for rapid assessment are reported in the literature. We tested a rapid and relatively cheap approach, taking the Dutch debate on Intensive Animal Production Systems (IAPS) and health as an example. Dutch policy-oriented publications on IAPS and health and ten semi-structured in-depth interviews with a variety of stakeholders were analyzed to identify stakeholders and concerns involved in the Dutch debate about IAPS and health. Concerns were mapped and a stakeholder network was derived. Three classes of concerns were recognized in the discussions about IAPS and health: concerns related to health risks, concerns regarding the activity causing the risks (IAPS), and concerns about the process to control the risks. The notions of 'trust' and 'scientific uncertainty' appeared as important themes in the discussions. Argumentation based on concerns directly related to health risks, the activity causing the risk (IAPS), and its risk management can easily become muddled up in a societal debate, limiting the development of effective action perspectives. Acknowledging these multiple stakeholder concerns can clarify the positions taken by stakeholders and allow for more and other action perspectives to develop.
    • Real-time Estimation of Epidemiologic Parameters from Contact Tracing Data During an Emerging Infectious Disease Outbreak.

      Soetens, Loes; Klinkenberg, Don; Swaan, Corien; Hahné, Susan; Wallinga, Jacco (2018-03)
      Contact tracing can provide accurate information on relevant parameters of an ongoing emerging infectious disease outbreak. This is crucial to investigators seeking to control such an outbreak. However, crude contact tracing data are difficult to interpret and methods for analyzing these data are scarce. We present a method to estimate and visualize key outbreak parameters from contact tracing information in real time by taking into account data censoring.
    • Recommendation on test readiness criteria for new approach methods in toxicology: Exemplified for developmental neurotoxicity.

      Bal-Price, Anna; Hogberg, Helena T; Crofton, Kevin M; Daneshian, Mardas; FitzGerald, Rex E; Fritsche, Ellen; Heinonen, Tuula; Hougaard Bennekou, Susanne; Klima, Stefanie; Piersma, Aldert H; Sachana, Magdalini; Shafer, Timothy J; Terron, Andrea; Monnet-Tschudi, Florianne; Viviani, Barbara; Waldmann, Tanja; Westerink, Remco H S; Wilks, Martin F; Witters, Hilda; Zurich, Marie-Gabrielle; Leist, Marcel (2018-02-23)
      Multiple non-animal-based test methods have never been formally validated. In order to use such new approach methods (NAMs) in a regulatory context, criteria to define their readiness are necessary. The field of developmental neurotoxicity (DNT) testing is used to exemplify the application of readiness criteria. The costs and number of untested chemicals are overwhelming for in vivo DNT testing. Thus, there is a need for inexpensive, high-throughput NAMs, to obtain initial information on potential hazards, and to allow prioritization for further testing. A background on the regulatory and scientific status of DNT testing is provided showing different types of test readiness levels, depending on the intended use of data from NAMs. Readiness criteria, compiled during a stakeholder workshop, uniting scientists from academia, industry and regulatory authorities are presented. An important step beyond the listing of criteria, was the suggestion for a preliminary scoring scheme. On this basis a (semi)-quantitative analysis process was assembled on test readiness of 17 NAMs with respect to various uses (e.g. prioritization/screening, risk assessment). The scoring results suggest that several assays are currently at high readiness levels. Therefore, suggestions are made on how DNT NAMs may be assembled into an integrated approach to testing and assessment (IATA). In parallel, the testing state in these assays was compiled for more than 1000 compounds. Finally, a vision is presented on how further NAM development may be guided by knowledge of signaling pathways necessary for brain development, DNT pathophysiology, and relevant adverse outcome pathways (AOP).
    • Recommendations for enterovirus diagnostics and characterisation within and beyond Europe.

      Harvala, Heli; Broberg, Eeva; Benschop, Kimberley; Berginc, Natasa; Ladhani, Shamez; Susi, Petri; Christiansen, Claus; McKenna, James; Allen, David; Makiello, Phoebe; McAllister, Georgina; Carmen, Mirabelli; Zakikhany, Katherina; Dyrdak, Robert; Nielsen, Xiaohui; Madsen, Tina; Paul, Joel; Moore, Catherine; von Eije, Karin; Piralla, Antonio; Carlier, Mieke; Vanoverschelde, Laura; Poelman, Randy; Anton, Andrés; López-Labrador, F Xavier; Pellegrinelli, Laura; Keeren, Kathrin; Maier, Melanie; Cassidy, Hayley; Derdas, Stavros; Savolainen-Kopra, Carita; Diedrich, Sabine; Nordbø, Svein; Buesa, Javier; Bailly, Jean-Luc; Baldanti, Fausto; MacAdam, Andrew; Mirand, Audrey; Dudman, Susanne; Schuffenecker, Isabelle; Kadambari, Seilesh; Neyts, Johan; Griffiths, Michael J; Richter, Jan; Margaretto, Cristina; Govind, Sheila; Morley, Ursula; Adams, Ortwin; Krokstad, Sidsel; Dean, Jonathan; Pons-Salort, Margarita; Prochazka, Birgit; Cabrerizo, Maria; Majumdar, Manasi; Nebbia, Gaia; Wiewel, Maryse; Cottrell, Simon; Coyle, Peter; Martin, Javier; Moore, Catrin; Midgley, Sofie; Horby, Peter; Wolthers, Katja; Simmonds, Peter; Niesters, Hubert; Fischer, Thea K (2018-02-06)
      Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European level. In order to improve EV diagnostics, collate data on severe EV infections and monitor the circulation of EV types, we have established European non-polio enterovirus network (ENPEN). First task of this cross-border network has been to ensure prompt and adequate diagnosis of these infections in Europe, and hence we present recommendations for non-polio EV detection and typing based on the consensus view of this multidisciplinary team including experts from over 20 European countries. We recommend that respiratory and stool samples in addition to cerebrospinal fluid (CSF) and blood samples are submitted for EV testing from patients with suspected neurological infections. This is vital since viruses like EV-D68 are rarely detectable in CSF or stool samples. Furthermore, reverse transcriptase PCR (RT-PCR) targeting the 5'noncoding regions (5'NCR) should be used for diagnosis of EVs due to their sensitivity, specificity and short turnaround time. Sequencing of the VP1 capsid protein gene is recommended for EV typing; EV typing cannot be based on the 5'NCR sequences due to frequent recombination events and should not rely on virus isolation. Effective and standardized laboratory diagnostics and characterisation of circulating virus strains are the first step towards effective and continuous surveillance activities, which in turn will be used to provide better estimation on EV disease burden.
    • Recommendations for newborn screening for galactokinase deficiency: A systematic review and evaluation of Dutch newborn screening data.

      Stroek, Kevin; Bouva, Marelle J; Schielen, Peter C J I; Vaz, Frédéric M; Heijboer, Annemieke C; de Jonge, Robert; Boelen, Anita; Bosch, Annet M (2018-03-21)
      Galactokinase (GALK) deficiency causes cataract leading to severe developmental consequences unless treated early. Because of the easy prevention and rapid reversibility of cataract with treatment, the Dutch Health Council advised to include GALK deficiency in the Dutch newborn screening program. The aim of this study is to establish the optimal screening method and cut-off value (COV) for GALK deficiency screening by performing a systematic review of the literature of screening strategies and total galactose (TGAL) values and by evaluating TGAL values in the first week of life in a cohort of screened newborns in the Netherlands.
    • Recommendations of the VAC2VAC workshop on the design of multi-centre validation studies.

      Halder, Marlies; Depraetere, Hilde; Delannois, Frédérique; Akkermans, Arnoud; Behr-Gross, Marie-Emmanuelle; Bruysters, Martijn; Dierick, Jean-François; Jungbäck, Carmen; Kross, Imke; Metz, Bernard; Pennings, Jeroen; Rigsby, Peter; Riou, Patrice; Balks, Elisabeth; Dobly, Alexandre; Leroy, Odile; Stirling, Catrina (2018-01-25)
      Within the Innovative Medicines Initiative 2 (IMI 2) project VAC2VAC (Vaccine batch to vaccine batch comparison by consistency testing), a workshop has been organised to discuss ways of improving the design of multi-centre validation studies and use the data generated for product-specific validation purposes. Moreover, aspects of validation within the consistency approach context were addressed. This report summarises the discussions and outlines the conclusions and recommendations agreed on by the workshop participants.
    • Reconsideration ICF scheme.

      Heerkens, Yvonne F; de Weerd, Marjolein; Huber, Machteld; de Brouwer, Carin P M; van der Veen, Sabina; Perenboom, Rom J M; van Gool, Coen H; Ten Napel, Huib; van Bon-Martens, Marja; Stallinga, Hillegonda A; van Meeteren, Nico L U (2018-01)
    • Reconstructed human epidermis models for irritant testing of medical devices.

      De Jong, Wim H; Coleman, Kelly P; Blaauboer, Bas J (2018-01-22)
    • Recovery of Previously Uncultured Bacterial Genera from Three Mediterranean Sponges.

      Versluis, Dennis; McPherson, Kyle; van Passel, Mark W J; Smidt, Hauke; Sipkema, Detmer (2017-10)
      Sponges often harbour a dense and diverse microbial community. Presently, a large discrepancy exists between the cultivable bacterial fraction from sponges and the community in its natural environment. Here, we aimed to acquire additional insights into cultivability of (previously uncultured) bacteria from three sponge species, namely Aplysina aerophoba, Corticium candelabrum and Petrosia ficiformis, by studying bacterial growth on five media in the form of 60 communities scraped from plates without antibiotics, as well as in the form of individual isolates that were grown on these media supplemented with antibiotics. We applied (double-)barcoded 16S ribosomal RNA (rRNA) gene amplicon sequencing for species identification. We show that previously uncultured bacteria can be cultivated using conventional plating and that application of antibiotics in the media can serve to capture a greater bacterial diversity. Moreover, we present criteria to address an important caveat of the plate scraping method whereby bacteria may be detected that did not actually grow. Fourteen out of 27 cultivated novel taxa (<95% identity of the 16S rRNA gene amplicon to reported species) belong to Actinobacteria, which indicates the presence of a large untapped reservoir of bioactive compounds. Three Flavobacteriaceae spp. were isolated that potentially constitute two new genera and one new species.
    • Reducing GHG emissions while improving diet quality: exploring the potential of reduced meat, cheese and alcoholic and soft drinks consumption at specific moments during the day.

      van de Kamp, Mirjam E; Seves, S Marije; Temme, Elisabeth H M (2018-02-20)
      The typical Western diet is associated with high levels of greenhouse gas (GHG) emissions and with obesity and other diet-related diseases. This study aims to determine the impact of adjustments to the current diet at specific moments of food consumption, to lower GHG emissions and improve diet quality.
    • The reduction of measles transmission during school vacations.

      Klinkenberg, Don; Hahné, Susan Jm; Woudenberg, Tom; Wallinga, Jacco (2018-04-06)
      Historically, measles incidence has shown clear seasonal patterns driven by the school calendar, but since the start of mass vaccination in developed countries there are only occasional outbreaks, which may have changed the effect of school vacations on transmission. In 2013-2014 a large measles epidemic took place in a low vaccination coverage area in The Netherlands, allowing us to quantify current-day measles transmission and the effect of school vacations.
    • The regulatory challenge of chemicals in the environment: Toxicity testing, risk assessment, and decision-making models.

      McCarty, L S; Borgert, C J; Posthuma, L (2018-11)
      Environmental assessment for chemicals relies on models of fate, exposure, toxicity, risk, and impacts. Together, these models should provide scientific support for regulatory risk management decision-making, assuming that progress through the data-information-knowledge-wisdom (DIKW) hierarchy is both appropriate and sufficient. Improving existing regulatory processes necessitates continuing enhancement of interpretation and evaluation of key data for use in decision-making schemes, including ecotoxicity testing data, physical-chemical properties, and environmental fate processes. Yet, as environmental objectives also increase in scope and sophistication to encompass a safe chemical economy, testing, risk assessment, and decision-making are subject to additional complexity due to the ongoing interaction between science and policy models. Problems associated with existing design and implementation choices in science and policy have both limited needed development beyond chemo-centric environmental risk assessment modeling and constrained needed improvements in environmental decision-making. Without a thorough understanding of either the scientific foundations or the disparate evaluation processes for validation, quality, and relevance, this results in complex technical and philosophical problems that increase costs and decrease productivity. Both over- and under-management of chemicals are consequences of failure to validate key model assumptions, unjustified standardized views on data selection, and inordinate reification (i.e., abstract concepts are wrongly treated as facts).
    • The relative invasive disease potential of Streptococcus pneumoniae among children after PCV introduction: a systematic review and meta-analysis.

      Balsells, Evelyn; Dagan, Ron; Yildirim, Inci; Gounder, Prabhu P; Steens, Anneke; Muñoz-Almagro, Carmen; Mameli, Chiara; Kandasamy, Rama; Lavi, Noga Givon; Daprai, Laura; van der Ende, Arie; Trzciński, Krzysztof; Nzenze, Susan; Meiring, Susan; Foster, Dona; Bulkow, Lisa R; Rudolph, Karen; Valero-Rello, Ana; Ducker, Struan; Vestrheim, Didrik Frimann; von Gottberg, Anne; Pelton, Stephen I; Zuccotti, GianVincenzo; Pollard, Andrew J; Sanders, Elisabeth A M; Campbell, Harry; Madhi, Shabir A; Nair, Harish; Kyaw, Moe H (2018-06-29)
      Burden of pneumococcal disease depends on the prevalence and invasive disease potential of serotypes. We aimed to estimate the invasive disease potential of serotypes in children under 5 years of age by combining data from different settings with routine immunisation with pneumococcal conjugate vaccines (PCV).
    • Remarkable spatial variation in the seroprevalence of Coxiella burnetii after a large Q fever epidemic.

      Pijnacker, Roan; Reimerink, Johan; Smit, Lidwien A M; van Gageldonk-Lafeber, Arianne B; Zock, Jan-Paul; Borlée, Floor; Yzermans, Joris; Heederik, Dick J J; Maassen, Catharina B M; van der Hoek, Wim (2017)
      Prior to the 2007-2010 Q fever epidemic in the Netherlands, the seroprevalence of antibodies against Coxiella burnetii in the general population was 1.5%, which is low compared to other countries. We aimed to determine the seroprevalence after the Q fever epidemic among people living in the affected area, compare the seroprevalence with the incidence of Q fever notifications during the 2007-2010 Q fever epidemic, and to identify farm exposures associated with having antibodies against C. burnetii.