• Objectively measured physical activity of hospital shift workers.

      Loef, Bette; van der Beek, Allard J; Holtermann, Andreas; Hulsegge, Gerben; van Baarle, Debbie; Proper, Karin I (2018-01-22)
      Objectives Shift work may alter workers' leisure-time and occupational physical activity (PA) levels, which might be one of the potential underlying mechanisms of the negative health effects of shift work. Therefore, we compared objectively measured PA levels between hospital shift and non-shift workers. Methods Data were used from Klokwerk+, a cohort study examining the health effects of shift work among healthcare workers employed in hospitals. In total, 401 shift workers and 78 non-shift workers were included, all of whom wore Actigraph GT3X accelerometers for up to seven days. Time spent sedentary, standing, walking, running, stairclimbing, and cycling during leisure time and at work was estimated using Acti4 software. Linear regression was used to compare proportions of time spent in these activities between hospital shift and non-shift workers. Results Average accelerometer wear-time was 105.9 [standard deviation (SD) 14.0] waking hours over an average of 6.9 (SD 0.6) days. No differences between hospital shift and non-shift workers were found in leisure-time PA (P>0.05). At work, shift workers were less sedentary [B=-10.6% (95% CI -14.3- -6.8)] and spent larger proportions of time standing [B=9.5% (95% CI 6.4-12.6)] and walking [B=1.2% (95% CI 0.1-2.2)] than non-shift workers. However, these differences in occupational PA became smaller when the number of night shifts during accelerometer wear-time increased. Conclusions Leisure-time PA levels of hospital shift workers were similar to those of non-shift workers, but shift workers were less sedentary and more physically active (ie, standing/walking) at work. Future research to the role of occupational activities in the health effects of shift work is recommended.
    • Occupational exposure to electromagnetic fields from medical sources.

      Stam, Rianne; Yamaguchi-Sekino, Sachiko (2018-04-07)
      High exposures to electromagnetic fields (EMF) can occur near certain medical devices in the hospital environment. A systematic assessment of medical occupational EMF exposure could help to clarify where more attention to occupational safety may be needed. This paper seeks to identify sources of high exposure for hospital workers and compare the published exposure data to occupational limits in the European Union. A systematic search for peer-reviewed publications was conducted via PubMed and Scopus databases. Relevant grey literature was collected via a web search. For each publication, the highest measured magnetic flux density or internal electric field strength per device and main frequency component was extracted. For low frequency fields, high action levels may be exceeded for magnetic stimulation, MRI gradient fields and movement in MRI static fields. For radiofrequency fields, the action levels may be exceeded near devices for diathermy, electrosurgery and hyperthermia and in the radiofrequency field inside MRI scanners. The exposure limit values for internal electric field may be exceeded for MRI and magnetic stimulation. For MRI and magnetic stimulation, practical measures can limit worker exposure. For diathermy, electrosurgery and hyperthermia, additional calculations are necessary to determine if SAR limits may be exceeded in some scenarios.
    • Occurrence and Nature of Double Alleles in Variable-Number Tandem-Repeat Patterns of More than 8,000 Mycobacterium tuberculosis Complex Isolates in The Netherlands.

      Jajou, Rana; Kamst, Miranda; van Hunen, Rianne; de Zwaan, Carolina Catherina; Mulder, Arnout; Supply, Philip; Anthony, Richard; van der Hoek, Wim; van Soolingen, Dick (2018-02)
      Since 2004, variable-number tandem-repeat (VNTR) typing of Mycobacterium tuberculosis complex isolates has been applied on a structural basis in The Netherlands to study the epidemiology of tuberculosis (TB). Although this technique is faster and technically less demanding than the previously used restriction fragment length polymorphism (RFLP) typing, reproducibility remains a concern. In the period from 2004 to 2015, 8,532 isolates were subjected to VNTR typing in The Netherlands, with 186 (2.2%) of these exhibiting double alleles at one locus. Double alleles were most common in loci 4052 and 2163b. The variables significantly associated with double alleles were urban living (odds ratio [OR], 1.503; 95% confidence interval [CI], 1.084 to 2.084; P = 0.014) and pulmonary TB (OR, 1.703; 95% CI, 1.216 to 2.386; P = 0.002). Single-colony cultures of double-allele strains were produced and revealed single-allele profiles; a maximum of five single nucleotide polymorphisms (SNPs) was observed between the single- and double-allele isolates from the same patient when whole-genome sequencing (WGS) was applied. This indicates the presence of two bacterial populations with slightly different VNTR profiles in the parental population, related to genetic drift. This observation is confirmed by the fact that secondary cases from TB source cases with double-allele isolates sometimes display only one of the two alleles present in the source case. Double alleles occur at a frequency of 2.2% in VNTR patterns in The Netherlands. They are caused by biological variation rather than by technical aberrations and can be transmitted either as single- or double-allele variants.
    • Oncology drugs in the crosshairs of pharmaceutical crime.

      Venhuis, Bastiaan J; Oostlander, Angela E; Giorgio, Domenico Di; Mosimann, Ruth; du Plessis, Ines (2018-04)
      Oncology drugs clearly have become a target for pharmaceutical crime. In 2016, falsified oncology drugs ranked fifth in the most commonly falsified drug category among the reports received by the Pharmaceutical Security Institute. Although the prevalence of illicit oncology drugs in the legal supply chains appears to be small, these drugs are difficult to detect, particularly in clinical practice. Forthcoming countermeasures to detect illicit drugs in high-income countries include compulsory antitampering devices and product verification technology for a risk-based selection of medicines. Health-care professionals must implement these new procedures into their workflow and remain vigilant about those medicines that are not selected. Although countermeasures should firmly tighten supply chain security, there are concerns about how quickly pharmaceutical crime will adapt to these protections. Because patients and health-care professionals have shown a lenient attitude towards purchasing medicines from unreliable sources, measures against the highly accessible illegal medicine supply chain remain necessary. To improve detectability in clinical practice, reporting of ineffectiveness and unusual drug effects as adverse events or adverse drug reactions is essential.
    • One health-samenwerking in de aanpak van psittacose

      Heijne M; Hogerwerf L; Dijkstra F; Goot J van der; Heddema E; Kroneman A; Notermans D; Pannekoek, Y; Rosa M de; Wierik M te; Giessen J van der; Roest HJ; Hoek W van der (2017-07)
    • An Opinion on non-human primates testing in Europe

      Epstein, Michelle M.; Vermeire, Theo (2017-10)
    • Opsonic Phagocytosis in Chronic Obstructive Pulmonary Disease is Enhanced by Nrf2 Agonists.

      Bewley, Martin A; Budd, Richard C; Ryan, Eilise; Cole, Joby; Collini, Paul; Marshall, Jennifer; Kolsum, Umme; Beech, Gussie; Emes, Richard D; Tcherniaeva, Irina; Berbers, Guy A M; Walmsley, Sarah R; Donaldson, Gavin; Wedzicha, Jadwiga A; Kilty, Iain; Rumsey, William; Sanchez, Yolanda; Brightling, Christopher E; Donnelly, Louise E; Barnes, Peter J; Singh, Dave; Whyte, Moira K B; Dockrell, David H (2018-03-16)
      Previous studies have identified defects in bacterial phagocytosis by alveolar macrophages (AM) in patients with chronic obstructive pulmonary disease (COPD) but the mechanisms and clinical consequences remain incompletely defined.
    • Het opsporen van foutpositieve Mycobacterium tuberculosis complex-kweken met DNA-fingerprinting

      Soolingen D van; Hunen R van; Vries G de; Ingen J van; Scholing M; Ott A; Kamst M (2017-07)
    • Optimising pain management in children with acute otitis media through a primary care-based multifaceted educational intervention: study protocol for a cluster randomised controlled trial.

      van Uum, Rick T; Venekamp, Roderick P; Sjoukes, Alies; van de Pol, Alma C; de Wit, G Ardine; Schilder, Anne G M; Damoiseaux, Roger A M J (2018-09-17)
      Whilst current guidelines highlight the importance of pain management for children with acute otitis media (AOM), there is evidence to suggest that this is not implemented in everyday practice. We have developed a primary care-based multifaceted educational intervention to optimise pain management in children with AOM, and we trial its clinical and cost effectiveness.
    • Optimising SME Potential in Modern Healthcare Systems: Challenges, Opportunities and Policy Recommendations.

      Horgan, Denis; van Kranen, Henk J; Morré, Servaas A (2018-08-24)
      The expansion of European small and medium-sized enterprises (SMEs) into the healthcare innovation arena suggests that this should be an important EU policy priority that can significantly benefit the economy, society and citizens, including patients. Deepening and widening of Europe's SMEs' growth and activities is part of the EU objectives as set out by the European Commission in its Communications "Small Business Act" for Europe [1] and "Small Business, Big World" [2]. However, innovative healthcare SMEs have struggled to get traction despite the sector being worth more than EUR 250 billion. The 1991 Maastricht Treaty gave the Union new competences in public health and more scope for cross-border cooperation in this area [3]. Nevertheless, health initiatives here have tripped over each other, due to the fact that the delivery of healthcare is a national competence [4]. As such, EU healthcare-driven policy has never truly found its footing as a singular policy area despite the fact that a tenth of the EU's GDP is spent on healthcare and more than 17 million people are employed in Europe in this sector [5]. Taking into account the necessity of bringing innovation into healthcare, and the willingness of SMEs to undertake the risk to be at the forefront of it, there is a need for a renewed effort to support SMEs so as to provide solutions for citizens and patients throughout the bloc in different healthcare settings [6]. This policy paper brings together two separate strands of analysis: firstly, a policy review of the main challenges and opportunities; secondly, a proposal for policy recommendations.
    • Oral bioaccessibility of silver nanoparticles and ions in natural soils: Importance of soil properties.

      Dang, Fei; Jiang, Yuanyuan; Li, Min; Zhong, Huan; Peijnenburg, WillieJ G M; Shi, Weilin; Zhou, Dongmei (2018-12)
      The abundance of silver nanoparticles (AgNPs) in consumer products has led to their environmental release and therefore to concern about their impact on human health. The ingestion of AgNP-contaminated soil from urban sites is an important exposure pathway, especially for children. Given the limited information on oral bioaccessibility of soil Ag, we used a physiologically based extraction test (PBET) to evaluate the bioaccessibility of AgNPs and AgNO3 from soil digestion. The AgNPs underwent several biochemical transformations, including their simultaneous dissolution and agglomeration in gastric fluid followed by the disintegration in the intestinal fluid of the agglomerates into NPs containing silver and chlorine. Therefore, Ag-containing soil exposed the intestine to nanoparticulate Ag in forms that were structurally different from the original forms. The bioaccessibility of AgNPs (0.5 ± 0.05%-10.9 ± 0.7%) was significantly lower than that of AgNO3 (4.7 ± 0.6%-14.4 ± 0.1%), as a result of the lower adsorption of nanoparticles to soil residues during the digestive process. For the soils tested, the bioaccessibility of AgNPs increased with decreasing clay contents and lower pH. By identifying the soil properties that control AgNP bioaccessibility, a more efficient and accurate screening can be performed of soil types that pose the greatest health risk associated with AgNP exposure.
    • Organic food consumption during pregnancy and its association with health-related characteristics: the KOALA Birth Cohort Study.

      Simões-Wüst, Ana Paula; Moltó-Puigmartí, Carolina; Jansen, Eugene Hjm; van Dongen, Martien Cjm; Dagnelie, Pieter C; Thijs, Carel (2017-08)
      To investigate the associations of organic food consumption with maternal pre-pregnancy BMI, hypertension and diabetes in pregnancy, and several blood biomarkers of pregnant women.
    • Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and an approach for their re-evaluation.

      Boobis, Alan; Brown, Paul; Cronin, Mark Timothy David; Edwards, James; Galli, Corrado Lodovico; Goodman, Jay; Jacobs, Abigail; Kirkland, David; Luijten, Mirjam; Marsaux, Cyril; Martin, Matthew; Yang, Chihae; Hollnagel, Heli Miriam (2017-09)
      The threshold of toxicological concern (TTC) approach is a resource-effective de minimis method for the safety assessment of chemicals, based on distributional analysis of the results of a large number of toxicological studies. It is being increasingly used to screen and prioritize substances with low exposure for which there is little or no toxicological information. The first step in the approach is the identification of substances that may be DNA-reactive mutagens, to which the lowest TTC value is applied. This TTC value was based on the analysis of the cancer potency database and involved a number of assumptions that no longer reflect the state-of-the-science and some of which were not as transparent as they could have been. Hence, review and updating of the database is proposed, using inclusion and exclusion criteria reflecting current knowledge. A strategy for the selection of appropriate substances for TTC determination, based on consideration of weight of evidence for genotoxicity and carcinogenicity is outlined. Identification of substances that are carcinogenic by a DNA-reactive mutagenic mode of action and those that clearly act by a non-genotoxic mode of action will enable the protectiveness to be determined of both the TTC for DNA-reactive mutagenicity and that applied by default to substances that may be carcinogenic but are unlikely to be DNA-reactive mutagens (i.e. for Cramer class I-III compounds). Critical to the application of the TTC approach to substances that are likely to be DNA-reactive mutagens is the reliability of the software tools used to identify such compounds. Current methods for this task are reviewed and recommendations made for their application.
    • Outbreak of diarrhoea among participants of a triathlon and a duathlon on 12 July 2015 in Utrecht, the Netherlands.

      Parkkali, S; Joosten, R; Fanoy, E; Pijnacker, R; VAN Beek, J; Brandwagt, D; VAN Pelt, W (2017-07)
      On 12 July 2015, a triathlon competition with 900 participants took place in Utrecht, the Netherlands. An outbreak investigation was initiated after 56 participants reported health complaints. An online questionnaire was sent to 700 participants. Stool specimens from six participants and four water specimens were collected from the swimming location. A total of 239 participants completed the questionnaire (response rate: 34%), 73 (31%) of them met the case definition for acute gastrointestinal illness (AGI). A total of 67% of the respondents were male and the median age was 38 years. Almost half (42%) of swimmers reported health complaints. Consumption of energy drinks and ingesting ⩾3 mouthfuls of canal water were identified as risk factors for AGI among swimmers only (adjusted relative risks (aRR) 1·6; 95% confidence intervals (CI) 1·0-2·5 and aRR 2·6; 95% CI 1·5-4·8). The collected water specimens tested positive for norovirus genogroup I and rotavirus and stool specimens tested positive for norovirus genogroup II. Our findings indicate that the outbreak could have been caused by exposure to norovirus during swimming. Swimmers should get information about the health risks for making an informed choice about participating. For future events, the organisers decided to change the swimming location from a canal to a recreational lake.
    • Outbreak of NDM-1-Producing Klebsiella pneumoniae in a Dutch Hospital, with Interspecies Transfer of the Resistance Plasmid and Unexpected Occurrence in Unrelated Health Care Centers.

      Bosch, Thijs; Lutgens, Suzanne P M; Hermans, Mirjam H A; Wever, Peter C; Schneeberger, Peter M; Renders, Nicole H M; Leenders, Alexander C A P; Kluytmans, Jan A J W; Schoffelen, Annelot; Notermans, Daan; Witteveen, Sandra; Bathoorn, Erik; Schouls, Leo M (2017-08)
      In the Netherlands, the number of cases of infection with New Delhi metallo-beta-lactamase (NDM)-positive Enterobacteriaceae is low. Here, we report an outbreak of NDM-1-producing Klebsiella pneumoniae infection in a Dutch hospital with interspecies transfer of the resistance plasmid and unexpected occurrence in other unrelated health care centers (HCCs). Next-generation sequencing was performed on 250 carbapenemase-producing Enterobacteriaceae isolates, including 42 NDM-positive isolates obtained from 29 persons at the outbreak site. Most outbreak isolates were K. pneumoniae (n = 26) and Escherichia coli (n = 11), but 5 isolates comprising three other Enterobacteriaceae species were also cultured. The 26 K. pneumoniae isolates had sequence type 873 (ST873), as did 7 unrelated K. pneumoniae isolates originating from five geographically dispersed HCCs. The 33 ST873 isolates that clustered closely together using whole-genome multilocus sequence typing (wgMLST) carried the same plasmids and had limited differences in the resistome. The 11 E. coli outbreak isolates showed great variety in STs, did not cluster using wgMLST, and showed considerable diversity in resistome and plasmid profiles. The blaNDM-1 gene-carrying plasmid present in the ST873 K. pneumoniae isolates was found in all the other Enterobacteriaceae species cultured at the outbreak location and in a single E. coli isolate from another HCC. We describe a hospital outbreak with an NDM-1-producing K. pneumoniae strain from an unknown source that was also found in patients from five other Dutch HCCs in the same time frame without an epidemiological link. Interspecies transfer of the resistance plasmid was observed in other Enterobacteriaceae species isolated at the outbreak location and in another HCC.
    • Outbreak of Salmonella Bovismorbificans associated with the consumption of uncooked ham products, the Netherlands, 2016 to 2017.

      Brandwagt, Diederik; van den Wijngaard, Cees; Tulen, Anna Dolores; Mulder, Annemieke Christine; Hofhuis, Agnetha; Jacobs, Rianne; Heck, Max; Verbruggen, Anjo; van den Kerkhof, Hans; Slegers-Fitz-James, Ife; Mughini-Gras, Lapo; Franz, Eelco (2018-01)
      In January 2017, an increase in reported Salmonellaenterica serotype Bovismorbificans cases in the Netherlands was observed since October 2016. We implemented a case-control study to identify the source, including all cases after December 2016. Adjusted odds ratios were calculated using logistic regression analysis. We traced back the distribution chain of suspected food items and sampled them for microbiological analysis. Human and food isolates were sequenced using whole genome sequencing (WGS). From October 2016 to March 2017, 54 S. Bovismorbificans cases were identified. Sequencing indicated that all were infected with identical strains. Twenty-four cases and 37 controls participated in the study. Cases were more likely to have consumed ham products than controls (aOR = 13; 95% CI: 2.0-77) and to have shopped at a supermarket chain (aOR = 7; 95% CI: 1.3-38). Trace-back investigations led to a Belgian meat processor: one retail ham sample originating from this processor tested positive for S. Bovismorbificans and matched the outbreak strain by WGS. All ham products related to the same batch were removed from the market to prevent further cases. This investigation illustrates the importance of laboratory surveillance for all Salmonella serotypes and the usefulness of WGS in an outbreak investigation.
    • Outpatient antibiotic use in Dutch infants after 10-valent pneumococcal vaccine introduction: a time-series analysis.

      Fortanier, Alexandre C; Venekamp, Roderick P; Stellato, Rebecca K; Sanders, Elisabeth A M; Damoiseaux, Roger A M J; Hoes, Arno W; Schilder, Anne M (2018-06-30)
      This population-based cohort study assesses the impact of switching from a 7-valent pneumococcal conjugate vaccine (PCV) to a 10-valent PCV on outpatient antibiotic use in Dutch infants, and whether geographical vaccination coverage modifies this association.
    • Ovarian cancer early detection by circulating CA125 in the context of anti-CA125 autoantibody levels: Results from the EPIC cohort.

      Fortner, Renée T; Schock, Helena; Le Cornet, Charlotte; Hüsing, Anika; Vitonis, Allison F; Johnson, Theron S; Fichorova, Raina N; Fashemi, Titilayo; Yamamoto, Hidemi S; Tjønneland, Anne; Hansen, Louise; Overvad, Kim; Boutron-Ruault, Marie-Christine; Kvaskoff, Marina; Severi, Gianluca; Boeing, Heiner; Trichopoulou, Antonia; Papatesta, Eleni-Maria; La Vecchia, Carlo; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Onland-Moret, N Charlotte; Peeters, Petra H; Bueno-de-Mesquita, H B As; Weiderpass, Elisabete; Quirós, J Ramón; Duell, Eric J; Sánchez, Maria-Jose; Navarro, Carmen; Ardanaz, Eva; Larrañaga, Nerea; Nodin, Björn; Jirström, Karin; Idahl, Annika; Lundin, Eva; Khaw, Kay-Tee; Travis, Ruth C; Gunter, Marc; Johansson, Mattias; Dossus, Laure; Merritt, Melissa A; Riboli, Elio; Terry, Kathryn L; Cramer, Daniel W; Kaaks, Rudolf (2018-04-01)
      CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non-cases. We investigated these objectives using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to four matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2-year lag-time intervals were calculated using conditional logistic regression calibrated toward the absolute risk estimates from a pre-existing epidemiological risk model as an offset-variable. Anti-CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti-CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76-0.92]; lowest tertile: 0.76 [0.67-0.86]; phet = 0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti-CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection.
    • Overall and Central Obesity and Risk of Lung Cancer: A Pooled Analysis.

      Yu, Danxia; Zheng, Wei; Johansson, Mattias; Lan, Qing; Park, Yikyung; White, Emily; Matthews, Charles E; Sawada, Norie; Gao, Yu-Tang; Robien, Kim; Sinha, Rashmi; Langhammer, Arnulf; Kaaks, Rudolf; Giovannucci, Edward L; Liao, Linda M; Xiang, Yong-Bing; Lazovich, DeAnn; Peters, Ulrike; Zhang, Xuehong; Bueno-de-Mesquita, Bas; Willett, Walter C; Tsugane, Shoichiro; Takata, Yumie; Smith-Warner, Stephanie A; Blot, William; Shu, Xiao-Ou (2018-03-06)
      The obesity-lung cancer association remains controversial. Concerns over confounding by smoking and reverse causation persist. The influence of obesity type and effect modifications by race/ethnicity and tumor histology are largely unexplored.