• Obeticholic acid ameliorates dyslipidemia but not glucose tolerance in mouse model of gestational diabetes.

      McIlvride, Saraid; Nikolova, Vanya; Fan, Hei Man; McDonald, Julie A K; Wahlström, Annika; Bellafante, Elena; Jansen, Eugene; Adorini, Luciano; Shapiro, David; Jones, Peter; et al. (2019-08-01)
      Metabolism alters markedly with advancing gestation, characterized by progressive insulin resistance, dyslipidemia, and raised serum bile acids. The nuclear receptor farnesoid X receptor (FXR) has an integral role in bile acid homeostasis and modulates glucose and lipid metabolism. FXR is known to be functionally suppressed in pregnancy. The FXR agonist, obeticholic acid (OCA), improves insulin sensitivity in patients with type 2 diabetes with nonalcoholic fatty liver disease. We therefore hypothesized that OCA treatment during pregnancy could improve disease severity in a mouse model of gestational diabetes mellitus (GDM). C57BL/6J mice were fed a high-fat diet (HFD; 60% kcal from fat) for 4 wk before and throughout pregnancy to induce GDM. The impact of the diet supplemented with 0.03% OCA throughout pregnancy was studied. Pregnant HFD-fed mice displayed insulin resistance and dyslipidemia. OCA significantly reduced plasma cholesterol concentrations in nonpregnant and pregnant HFD-fed mice (by 22.4%, P < 0.05 and 36.4%, P < 0.001, respectively) and reduced the impact of pregnancy on insulin resistance but did not change glucose tolerance. In nonpregnant HFD-fed mice, OCA ameliorated weight gain, reduced mRNA expression of inflammatory markers in white adipose tissue, and reduced plasma glucagon-like peptide 1 concentrations (by 62.7%, P < 0.01). However, these effects were not evident in pregnant mice. OCA administration can normalize plasma cholesterol levels in a mouse model of GDM. However, the absence of several of the effects of OCA in pregnant mice indicates that the agonistic action of OCA is not sufficient to overcome many metabolic consequences of the pregnancy-associated reduction in FXR activity.
    • 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.
    • Obstacle runs en infectieziekten: tips voor de GGD-praktijk

      Oorsprong DM; Boogert EM den; Buiting MP; Hondema LS; Ewalts H; Dam ASG van (2019-03)
    • 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.
    • Occupational risk of salmonellosis and campylobacteriosis: a nationwide population-based registry study.

      Duijster, Janneke W; Franz, Eelco; Neefjes, Jacques J C; Mughini-Gras, Lapo (2019-09-01)
      Person-level occupational data for all Dutch residents were linked to lab-confirmed salmonellosis and campylobacteriosis data, and to serological data from a previous national serosurvey. SIRs for salmonellosis and campylobacteriosis among occupational sectors and specific high-risk occupations were calculated based on the total employed population. Moreover, Salmonella and Campylobacter seroincidence rates were compared among sectors and high-risk occupations.
    • 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.
    • Occurrence of human papillomavirus (HPV) type replacement by sexual risk-taking behaviour group: Post-hoc analysis of a community randomized clinical trial up to nine years after vaccination (IV).

      Gray, Penelope; Luostarinen, Tapio; Vänskä, Simopekka; Eriksson, Tiina; Lagheden, Camilla; Man, Irene; Palmroth, Johanna; Pimenoff, Ville N; Söderlund-Strand, Anna; Dillner, Joakim; et al. (2019-02-05)
      Oncogenic non-vaccine human papillomavirus (HPV) types may conceivably fill the vacated ecological niche of the vaccine types. The likelihood of this may differ by the risk of acquiring HPV infections. We examined occurrence of HPV types among vaccinated and unvaccinated subgroups of 1992-1994 birth cohorts with differing acquisition risks up to 9 years post-implementation of HPV vaccination in 33 Finnish communities randomized to: Arm A (gender-neutral HPV16/18 vaccination), Arm B (girls-only HPV16/18 vaccination and hepatitis B-virus (HBV) vaccination of boys), and Arm C (gender-neutral HBV vaccination). Out of 1992-94 born resident boys (31,117) and girls (30,139), 8,618 boys and 15,615 girls were vaccinated respectively with 20-30% and 50% coverage in 2007-09. In 2010-13, 8,868 HPV16/18 and non-HPV vaccinated females, and in 2014-16, 5,574 originally or later (2010-13) HPV16/18 vaccinated females attended two cervical sampling visits, aged 18.5 and 22-years. The samples were typed for HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68 using PCR followed by MALDI-TOF MS. HPV prevalence ratios (PR) between Arms A/B vs C were calculated for Chlamydia trachomatis positives (core-group), and negatives (general population minus core group). At both visits the vaccine-protected HPV type PRs did not significantly differ between the core-group and non-core group. Among the vaccinated 18-year-olds, HPV51 occurrence was overall somewhat increased (PR
    • Occurrence of phthalate esters in the environment of The Netherlands.

      Peijnenburg, Willie J G M; Struijs, Jaap (2006-02-01)
      Overviews of levels of n-dibutylphthalate (DBP) and di(2-ethylhexyl)phthalate (DEHP) found in freshwater, marine water, sediment, and fish in the Netherlands are given. Sampling spanned a 9-month period (all seasons except winter) and allowed assessing whether phthalate levels are season dependent. Results obtained are compared to data reported for other Western European countries and a fugacity-based modeling approach is used to assess whether there is equilibrium among the various compartments. Highest levels of dissolved DBP and DEHP were found in freshwater samples, whereas these compounds were usually below the limit of detection (LOD) in marine water and sediment. Median levels were log-normally distributed; statistical analysis showed that sampling season is not a relevant determinant parameter. Similar results were obtained for the freshwater sediment compartment, with DEHP levels exceeding concentrations of DBP. DBP levels in fish were often below the LOD. Nevertheless, mean values around 1.8 microg kg(-1) wet fish were found for both DEHP and DBP. Fugacity calculations revealed that especially for DEHP there is no equilibrium among the compartments. DEHP emissions are directed to water, whereas the calculations reveal that sediments provide a sink for DEHP and there is net transport to air. Although it has been suggested that water is the primary compartment for DBP, fugacity plots suggest that air is the compartment to which emissions are directed dominantly. The data reported are in line with values found in Western Europe.
    • On the limits of toxicant-induced tolerance testing: cotolerance and response variation of antibiotic effects.

      Schmitt, Heike; Martinali, Bennie; Beelen, Patrick van; Seinen, Willem (2006-07-01)
      Pollution-induced community tolerance (PICT) as an ecotoxicological test system has been claimed to detect pollutant effects highly specifically and sensitively. However, the specificity might be limited by the occurrence of cotolerance. Another limitation of the application of any ecotoxicological test system lies in variation of the measured responses. We tested the variation and the occurrence of cotolerance experimentally, using antibiotics as toxicants, soil microcosms as microbial communities, and tolerance determination in Biolog plates as PICT detection test. Bacteria have been discussed as being prone to multiple tolerances due to the possible accumulation of multiple resistance genes on mobile genetic elements. However, in our experiments, cotolerance occurred only between antibiotics of the same group (oxytetracycline and tetracycline), as expected from their identical mode of action. Cotolerance between oxytetracycline and tylosin in soil microcosms exposed to oxytetracycline was low, as was cotolerance to oxytetracycline in tylosin-exposed microcosms. We conclude that tolerance development to antibiotics in soils reflects the actual selection pressure rather than a general pattern of multiple resistances. Concerning variation, the PICT effect of tetracycline was well reproducible in two consecutive years. The response variation linked to PICT experiments in controlled microcosms was comparable to that of ecotoxicological test systems of equivalent complexity. In conclusion, our results support an application of the PICT methodology as an effective means to study the soil ecotoxicology of antibiotics.
    • 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; Broek I van den; Pannekoek, Y; Broek I van den; Wierik M te; et al. (2017-07)
    • One-carbon metabolism biomarkers and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition.

      Vrieling, Alina; Bueno-De-Mesquita, H Bas; Ros, Martine M; Kampman, Ellen; Aben, Katja K; Büchner, Frederike L; Jansen, Eugène H; Roswall, Nina; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; et al. (2019-01-29)
      Published associations between dietary folate and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status. This nested case-control analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC) investigated associations between pre-diagnostic serum folate, homocysteine, vitamins B6 and B12 and the risk of urothelial cell carcinomas of the bladder (UCC). A total of 824 patients with newly diagnosed UCC were matched with 824 cohort members. Serum folate, homocysteine, and vitamins B6 and B12 were measured. Odds ratios (OR) and 95% confidence intervals (CI) for total, aggressive, and non-aggressive UCC were estimated using conditional logistic regression with adjustment for smoking status, smoking duration and intensity, and other potential confounders. Additionally, statistical interaction with smoking status was assessed. A halving in serum folate concentrations was moderately associated with risk of UCC (OR: 1.18; 95% CI: 0.98-1.43), in particular aggressive UCC (OR: 1.34; 95% CI: 1.02-1.75; p-heterogeneity = 0.19). Compared to never smokers in the highest quartile of folate concentrations, this association seemed only apparent among current smokers in the lowest quartile of folate concentrations (OR: 6.26; 95% CI: 3.62-10.81, p-interaction = 0.07). Dietary folate was not associated with aggressive UCC (OR: 1.26; 95% CI: 0.81-1.95; p-heterogeneity = 0.14). No association was observed between serum homocysteine, vitamins B6 and B12 and risk of UCC. This study suggests that lower serum folate concentrations are associated with increased UCC risk, in particular aggressive UCC. Residual confounding by smoking cannot be ruled out and these findings require confirmation in future studies with multiple measurements.
    • Op de loer in de modder en oppervlaktewater: Leptospira en Francisella tularensis

      Pijnacker R; Joosten R; Janse I; Brandwagt D; Fanoy E; Dam S van; Petrignani M; Weijden C van der; Schets F; Giessen J van der; et al. (2019-03)
    • 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; et al. (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

      Broek I van den; 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.