• H7N9 influenza split vaccine with SWE oil-in-water adjuvant greatly enhances cross-reactive humoral immunity and protection against severe pneumonia in ferrets.

      de Jonge, Jørgen; van Dijken, Harry; de Heij, Femke; Spijkers, Sanne; Mouthaan, Justin; de Jong, Rineke; Roholl, Paul; Adami, Eduardo Alfredo; Akamatsu, Milena Apetito; Ho, Paulo Lee; et al. (2020-01-01)
    • Haem iron intake and risk of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

      Ward, Heather A; Whitman, Julia; Muller, David C; Johansson, Mattias; Jakszyn, Paula; Weiderpass, Elisabete; Palli, Domenico; Fanidi, Anouar; Vermeulen, Roel; Tjønneland, Anne; et al. (2018-10-18)
      Epidemiological studies suggest that haem iron, which is found predominantly in red meat and increases endogenous formation of carcinogenic N-nitroso compounds, may be positively associated with lung cancer. The objective was to examine the relationship between haem iron intake and lung cancer risk using detailed smoking history data and serum cotinine to control for potential confounding.
    • Haemophilus is overrepresented in the nasopharynx of infants hospitalized with RSV infection and associated with increased viral load and enhanced mucosal CXCL8 responses.

      Ederveen, Thomas H A; Ferwerda, Gerben; Ahout, Inge M; Vissers, Marloes; de Groot, Ronald; Boekhorst, Jos; Timmerman, Harro M; Huynen, Martijn A; van Hijum, Sacha A F T; de Jonge, Marien I (2018-01-11)
      While almost all infants are infected with respiratory syncytial virus (RSV) before the age of 2 years, only a small percentage develops severe disease. Previous studies suggest that the nasopharyngeal microbiome affects disease development. We therefore studied the effect of the nasopharyngeal microbiome on viral load and mucosal cytokine responses, two important factors influencing the pathophysiology of RSV disease. To determine the relation between (i) the microbiome of the upper respiratory tract, (ii) viral load, and (iii) host mucosal inflammation during an RSV infection, nasopharyngeal microbiota profiles of RSV infected infants (< 6 months) with different levels of disease severity and age-matched healthy controls were determined by 16S rRNA marker gene sequencing. The viral load was measured using qPCR. Nasopharyngeal CCL5, CXCL10, MMP9, IL6, and CXCL8 levels were determined with ELISA.
    • The hallmarks of CMV-specific CD8 T-cell differentiation.

      van den Berg, Sara P H; Pardieck, Iris N; Lanfermeijer, Josien; Sauce, Delphine; Klenerman, Paul; van Baarle, Debbie; Arens, Ramon (2019-04-13)
      Upon cytomegalovirus (CMV) infection, large T-cell responses are elicited that remain high or even increase over time, a phenomenon named memory T-cell inflation. Besides, the maintained robust T-cell response, CMV-specific T cells seem to have a distinctive phenotype, characterized by an advanced differentiation state. Here, we will review this "special" differentiation status by discussing the cellular phenotype based on the expression of CD45 isoforms, costimulatory, inhibitory and natural killer receptors, adhesion and lymphocyte homing molecules, transcription factors, cytokines and cytotoxic molecules. In addition, we focus on whether the differentiation state of CMV-specific CD8 T cells is unique in comparison with other chronic viruses and we will discuss the possible impact of factors such as antigen exposure and aging on the advanced differentiation status of CMV-specific CD8 T cells.
    • Hand rub consumption and hand hygiene compliance are not indicators of pathogen transmission in intensive care units.

      Eckmanns, T; Schwab, F; Bessert, J; Wettstein, R; Behnke, M; Grundmann, Hajo; Rüden, H; Gastmeier, P (2006-08-01)
      The objective of this study was to investigate whether nosocomial infection (NI) rates, hand hygiene compliance rates and the amount of alcohol-based hand rub used for hand disinfection are useful indicators of pathogen transmission in intensive care units (ICUs), and whether they could be helpful in identifying infection control problems. All isolates of 10 of the most frequent pathogens from patients who were hospitalized in an ICU for >48 h were genotyped to identify transmission episodes in five ICUs. The incidence of transmission was correlated with hand hygiene compliance, hand rub consumption and NI rates. The incidence of transmission episodes varied between 2.8 and 6.8 in the five ICUs. The NI rate was 8.6-22.5 per 1000 patient-days, hand hygiene compliance was 30-47% and hand rub consumption was 57-102 L per 1000 patient-days. There was no correlation between the incidence of transmission episodes and hand rub consumption or hand hygiene compliance. The correlation between transmission rates and NI rates was 0.4 (P = 0.5), and with the exclusion of one ICU, it was 1 (P < 0.01). The incidence of NI is a relatively good indicator for the identification of pathogen transmissions, but hand rub consumption and hand hygiene compliance, at least with the relatively low level of compliance found in this study, are not indicators of pathogen transmission.
    • Hangijzer: autobanden op grasvelden

      de Vries, M; Kraaij-Dirkzwager, M (2019-05-10)
    • Hangijzer: Vaccinatie tegen HPV

      Timmermans, D (2019-05-10)
    • 'Happy the man, who, studying nature's laws, Thro' known effects can trace the secret cause.' Do we have enough pieces to solve the pyrazinamide puzzle?

      Anthony, R M; den Hertog, A L; van Soolingen, D (2018-03-08)
      A low pH was assumed to be required for the activity of pyrazinoic acid (the active form of pyrazinamide) against Mycobacterium tuberculosis, but recently activity has been demonstrated at neutral pH. Renewed interest in pyrazinamide has led to an increasing number of potential targets and the suspicion that pyrazinamide is a 'dirty drug'. However, it is our opinion that the recent demonstration that pyrazinoic acid is active against PanD provides an alternative explanation for the secret of pyrazinamide's unusual activity. In this article we propose that PanD is the primary target of pyrazinoic acid but expression of pyrazinoic acid susceptibility requires an intact stress response. As the mycobacterial stress response requires the interaction of a number of genes, disruption of any could result in an inability to enter the susceptible phenotype. We believe this model can explain most of the recent observations of the seemingly diverse spectrum of activity of pyrazinamide.
    • Harmonization of PCR-based detection of intestinal pathogens: experiences from the Dutch external quality assessment scheme on molecular diagnosis of protozoa in stool samples.

      Schuurs, Theo A; Koelewijn, Rob; Brienen, Eric A T; Kortbeek, Titia; Mank, Theo G; Mulder, Bert; Stelma, Foekje F; van Lieshout, Lisette; van Hellemond, Jaap J (2018-02-16)
      Real-time PCR methods are increasingly used in routine patient care settings not only to determine the presence or absence of pathogens in patient materials, but also to obtain semiquantitative results to estimate the pathogen load. However, it is so far unknown how well these methods are harmonized among different laboratories.
    • Harmonized methodology to assess chronic dietary exposure to residues from compounds used as pesticide and veterinary drug.

      Arcella, Davide; Boobis, Alan; Cressey, Peter; Erdely, Holly; Fattori, Vittorio; Leblanc, Jean-Charles; Lipp, Markus; Reuss, Rainer; Scheid, Stefan; Tritscher, Angelika; et al. (2019-03-28)
      Risk assessments for pesticide and veterinary drug residues in food are performed respectively by the Joint FAO/WHO Expert Meeting on Pesticide Residues (JMPR) and the Joint FAO/WHO Expert Committee on Food Additives (JECFA). The models used by the two Committees to assess chronic dietary exposure are based on different data and assumptions which may be confusing, particularly for risk managers, when the same compound is used to treat plants and animals. This publication details the results of combined chronic dietary exposure assessments for eight compounds used both as pesticide and veterinary drugs. It compares the results from models in use by JMPR and JECFA with those from national estimates performed by 17 countries. Results show that the JECFA model is better reflecting less than lifetime dietary exposure by considering consumption of children and high consumers. The JMPR model is a suitable model for estimating average chronic (lifetime) exposure to residues present in widely and regularly consumed staple commodities. However, it is suitable neither for estimating children's exposure nor more generally for assessing less than lifetime dietary exposure. In order to select the appropriate exposure model related to the occurrence of adverse effects i.e. effects occurring over less-than-lifetime or effects occurring only over lifetime, this paper proposes criteria to match the toxicological profile of the compound and the appropriate exposure scenarios. These approaches will continue to be harmonized to ensure the most scientifically sound basis for the risk assessment for pesticides and veterinary drug residues and consequently for other chemicals in food.
    • Harvesting the wisdom of the crowd: using online ratings to explore care experiences in regions.

      Hendrikx, Roy J P; Spreeuwenberg, Marieke D; Drewes, Hanneke W; Struijs, Jeroen N; Ruwaard, Dirk; Baan, Caroline A (2018-10-20)
      Regional population health management (PHM) initiatives need an understanding of regional patient experiences to improve their services. Websites that gather patient ratings have become common and could be a helpful tool in this effort. Therefore, this study explores whether unsolicited online ratings can provide insight into (differences in) patient's experiences at a (regional) population level.
    • Hazard classification of chemicals inducing haemolytic anaemia: An EU regulatory perspective.

      Muller, Andre; Jacobsen, Helene; Healy, Edel; McMickan, Sinead; Istace, Fréderique; Blaude, Marie-Noëlle; Howden, Peter; Fleig, Helmut; Schulte, Agnes (2006-08-01)
      Haemolytic anaemia is often induced following prolonged exposure to chemical substances. Currently, under EU Council Directive 67/548/EEC, substances which induce such effects are classified as dangerous and assigned the risk phrase R48 'Danger of serious damage to health by prolonged exposure.' Whilst the general classification criteria for this endpoint are outlined in Annex VI of this Directive, they do not provide specific information to assess haemolytic anaemia. This review produced by the EU Working Group on Haemolytic Anaemia provides a toxicological assessment of haemolytic anaemia and proposes criteria that can be used in the assessment for classification of substances which induce such effects. An overview of the primary and secondary effects of haemolytic anaemia which can occur in rodent repeated dose toxicity studies is given. A detailed analysis of the toxicological significance of such effects is then performed and correlated with the general classification criteria used for this endpoint. This review intends to give guidance when carrying out an assessment for classification for this endpoint and to allow for better transparency in the decision-making process on when to classify based on the presence of haemolytic anaemia in repeated dose toxicity studies. The extended classification criteria for haemolytic anaemia outlined in this review were accepted by the EU Commission Working Group on the Classification and Labelling of Dangerous Substances in September 2004.
    • Head skeleton malformations in zebrafish (Danio rerio) to assess adverse effects of mixtures of compounds.

      Staal, Yvonne C M; Meijer, Jeroen; van der Kris, Remco J C; de Bruijn, Annamaria C; Boersma, Anke Y; Gremmer, Eric R; Zwart, Edwin P; Beekhof, Piet K; Slob, Wout; van der Ven, Leo T M (2018-10-04)
      The EU-EuroMix project adopted the strategy of the European Food Safety Authority (EFSA) for cumulative risk assessment, which limits the number of chemicals to consider in a mixture to those that induce a specific toxicological phenotype. These so-called cumulative assessment groups (CAGs) are refined at several levels, including the target organ and specific phenotype. Here, we explore the zebrafish embryo as a test model for quantitative evaluation in one such CAG, skeletal malformations, through exposure to test compounds 0-120 hpf and alcian blue cartilage staining at 120 hpf, focusing on the head skeleton. Reference compounds cyproconazole, flusilazole, metam, and thiram induced distinctive phenotypes in the head skeleton between the triazoles and dithiocarbamates. Of many evaluated parameters, the Meckel's-palatoquadrate (M-PQ) angle was selected for further assessment, based on the best combination of a small confidence interval, an intermediate maximal effect size and a gentle slope of the dose-response curve with cyproconazole and metam. Additional test compounds included in the CAG skeletal malformations database were tested for M-PQ effects, and this set was supplemented with compounds associated with craniofacial malformations or cleft palate to accommodate otherwise organized databases. This additional set included hexaconazole, all-trans-retinoic acid, AM580, CD3254, maneb, pyrimethanil, imidacloprid, pirimiphos-methyl, 2,4-dinitrophenol, 5-fluorouracil, 17alpha-ethynylestradiol (EE2), ethanol, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), PCB 126, methylmercury, boric acid, and MEHP. Most of these compounds produced a dose-response for M-PQ effects. Application of the assay in mixture testing was provided by combined exposure to cyproconazole and TCDD through the isobole method, supporting that in this case the combined effect can be modeled through concentration addition.
    • Health and Economic Impact of a Tender-Based, Sex-Neutral Human Papillomavirus 16/18 Vaccination Program in the Netherlands.

      Qendri, Venetia; Bogaards, Johannes A; Berkhof, Johannes (2017-07-15)
      Uptake of human papillomavirus (HPV) vaccine among girls in the Dutch immunization program has plateaued at around 60%. Vaccinating boys may be an appealing complementary strategy for the prevention of HPV-related diseases, especially since tender negotiations and reduced dosing schemes have driven down the cost of vaccination.
    • Health assessments for health governance—concepts and methodologies

      Fehr, Rainer; Alexanderson, Kristina; Favaretti, Carlo; de Jong, Judith; La Torre, Giuseppe; Lim, Tek-Ang; Martin-Olmedo, Piedad; Mekel, Odile C L; Michelsen, Kai; Rosenkötter, Nicole; et al. (2017-08)
    • Health care costs in the last year of life--the Dutch experience.

      Polder, Johan J; Barendregt, Jan J; Oers, Hans van (2006-10-01)
      Health expenditure depends heavily on age. Common wisdom is that the age pattern is dominated by costs in the last year of life. Knowledge about these costs is important for the debate on the future development of health expenditure. According to the 'red herring' argument traditional projection methods overestimate the influence of ageing because improvements in life expectancy will postpone rather than raise health expenditure. This paper has four objectives: (1) to estimate health care costs in the last year of life in the Netherlands; (2) to describe age patterns and differences between causes of death for men and women; (3) to compare cost profiles of decedents and survivors; and (4) to use these figures in projections of future health expenditure. We used health insurance data of 2.1 million persons (13% of the Dutch population), linked at the individual level with data on the use of home care and nursing homes and causes of death in 1999. On average, health care costs amounted to 1100 Euro per person. Costs per decedent were 13.5 times higher and approximated 14,906 Euro in the last year of life. Most costs related to hospital care (54%) and nursing home care (19%). Among the major causes of death, costs were highest for cancer (19,000 Euro) and lowest for myocardial infarctions (8068 Euro). Between the other causes of death, however, cost differences were rather limited. On average costs for the younger decedents were higher than for people who died at higher ages. Ten per cent of total health expenditure was associated with the health care use of people in their last year of life. Increasing longevity will result in higher costs because people live longer. The decline of costs in the last year of life with increasing age will have a moderate lowering effect. Our projection demonstrated a 10% decline in the growth rate of future health expenditure compared to conventional projection methods.
    • Health impact assessment of a skin sensitizer: Analysis of potential policy measures aimed at reducing geraniol concentrations in personal care products and household cleaning products.

      Jongeneel, W P; Delmaar, J E; Bokkers, B G H (2018-09)
      A methodology to assess the health impact of skin sensitizers is introduced, which consists of the comparison of the probabilistic aggregated exposure with a probabilistic (individual) human sensitization or elicitation induction dose. The health impact of potential policy measures aimed at reducing the concentration of a fragrance allergen, geraniol, in consumer products is analysed in a simulated population derived from multiple product use surveys. Our analysis shows that current dermal exposure to geraniol from personal care and household cleaning products lead to new cases of contact allergy and induce clinical symptoms for those already sensitized. We estimate that this exposure results yearly in 34 new cases of geraniol contact allergy per million consumers in Western and Northern Europe, mainly due to exposure to household cleaning products. About twice as many consumers (60 per million) are projected to suffer from clinical symptoms due to re-exposure to geraniol. Policy measures restricting geraniol concentrations to <0.01% will noticeably reduce new cases of sensitization and decrease the number of people with clinical symptoms as well as the frequency of occurrence of these clinical symptoms. The estimated numbers should be interpreted with caution and provide only a rough indication of the health impact.
    • Health literacy among older adults is associated with their 10-years' cognitive functioning and decline - the Doetinchem Cohort Study.

      Geboers, Bas; Uiters, Ellen; Reijneveld, Sijmen A; Jansen, Carel J M; Almansa, Josué; Nooyens, Astrid C J; Verschuren, W M Monique; de Winter, Andrea F; Picavet, H Susan J (2018-03-20)
      Many older adults have low levels of health literacy which affects their ability to participate optimally in healthcare. It is unclear how cognitive decline contributes to health literacy. To study this, longitudinal data are needed. The aim of this study was therefore to assess the associations of cognitive functioning and 10-years' cognitive decline with health literacy in older adults.
    • Health literacy skills for informed decision making in colorectal cancer screening: Perceptions of screening invitees and experts.

      Woudstra, Anke J; Timmermans, Daniëlle R M; Uiters, Ellen; Dekker, Evelien; Smets, Ellen M A; Fransen, Mirjam P (2017-12-20)
      The process of informed decision making (IDM) requires an adequate level of health literacy. To ensure that all individuals have equal opportunity to make an informed decision in colorectal cancer (CRC) screening, it is essential to gain more insight into which health literacy skills are needed for IDM. Our aims were (i) to explore how individuals make a decision about CRC screening and (ii) to explore which skills are needed for IDM in CRC screening and (iii) to integrate these findings within a conceptual framework.