• Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries.

      Li, Sherly X; Imamura, Fumiaki; Schulze, Matthias B; Zheng, Jusheng; Ye, Zheng; Agudo, Antonio; Ardanaz, Eva; Aune, Dagfinn; Boeing, Heiner; Dorronsoro, Miren; et al. (2018-03-17)
      Gene-macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes.
    • Interpretation of CVD risk predictions in clinical practice: Mission impossible?

      Lagerweij, G R; Moons, K G M; de Wit, G A; Koffijberg, H (2019-01-01)
      Cardiovascular disease (CVD) risk prediction models are often used to identify individuals at high risk of CVD events. Providing preventive treatment to these individuals may then reduce the CVD burden at population level. However, different prediction models may predict different (sets of) CVD outcomes which may lead to variation in selection of high risk individuals. Here, it is investigated if the use of different prediction models may actually lead to different treatment recommendations in clinical practice. The exact definition of and the event types included in the predicted outcomes of four widely used CVD risk prediction models (ATP-III, Framingham (FRS), Pooled Cohort Equations (PCE) and SCORE) was determined according to ICD-10 codes. The models were applied to a Dutch population cohort (n = 18,137) to predict the 10-year CVD risks. Finally, treatment recommendations, based on predicted risks and the treatment threshold associated with each model, were investigated and compared across models. Due to the different definitions of predicted outcomes, the predicted risks varied widely, with an average 10-year CVD risk of 1.2% (ATP), 5.2% (FRS), 1.9% (PCE), and 0.7% (SCORE). Given the variation in predicted risks and recommended treatment thresholds, preventive drugs would be prescribed for 0.2%, 14.9%, 4.4%, and 2.0% of all individuals when using ATP, FRS, PCE and SCORE, respectively. Widely used CVD prediction models vary substantially regarding their outcomes and associated absolute risk estimates. Consequently, absolute predicted 10-year risks from different prediction models cannot be compared directly. Furthermore, treatment decisions often depend on which prediction model is applied and its recommended risk threshold, introducing unwanted practice variation into risk-based preventive strategies for CVD.
    • Intestinal antibody responses to a live oral poliovirus vaccine challenge among adults previously immunized with inactivated polio vaccine in Sweden.

      Brickley, Elizabeth B; Connor, Ruth I; Wieland-Alter, Wendy F; Collett, Marc S; Hartford, Marianne; van der Avoort, Harrie; Boesch, Austin W; Weiner, Joshua A; Ackerman, Margaret E; McKinlay, Mark A; et al. (2019-01-01)
    • Intestinal carriage of ampicillin- and vancomycin-resistant Enterococcus faecium in humans, dogs and cats in the Netherlands.

      van den Bunt, G; Top, J; Hordijk, J; de Greeff, S C; Mughini-Gras, L; Corander, J; van Pelt, W; Bonten, M J M; Fluit, A C; Willems, R J L (2017-12-25)
      The prevalence of ampicillin- and/or vancomycin-resistant Enterococcus faecium (AREf and VREf) has increased in hospitalized patients in the Netherlands.
    • Intoxication following minor stabs from the spines of a porcupine fish.

      Gorcum, Teetske F van; Janse, Max; Leenders, Marianne E C; Vries, Irma de; Meulenbelt, Jan (2006-06-01)
      We report an unusual intoxication by tetrodotoxin (TTX). A curator of an aquarium sustained minor punctures in his finger from the spines of a porcupine fish during an autopsy of a dead porcupine fish. He developed paresthesias, numbness, paresis, dizziness and headache. The death of the fish might have caused some autolysis, leading to increased availability of TTX. In combination with direct contact with the organ fluids, this probably led to TTX exposure via minor wounds.
    • Intraspecific genetic variation in and populations circulating in different geographical regions of Poland.

      Bilska-Zając, Ewa; Franssen, Frits; Różycki, Mirosław; Swart, Arno; Karamon, Jacek; Sroka, Jacek; Zdybel, Jolanta; Ziętek-Barszcz, Anna; Cencek, Tomasz (2019-12-01)
      Trichinella spiralis and Trichinella britovi are species of nematodes which are responsible for the majority of Trichinella infections in the world and the most prevalent in Poland. The most abundant species - T. spiralis, is considered to be more genetically homogeneous in Europe than T. britovi. The aim of the present study was to determine the genetic variability in T. spiralis and T. britovi populations based on nuclear 5S rDNA intergenic spacer region (5S rDNA) and cytochrome c oxidase 1 (COX1) gene sequences. For the study, 55 isolates of T. spiralis and 50 isolates of T. britovi isolated from wild boars, pigs, brown rat and a red fox were analyzed. Based on the analysis of both genes, the genetic variability within populations of T. spiralis and T. britovi differed. In T. spiralis, two single nucleotide polymorphisms (SNPs) were observed in the 612 bp 5S rDNA gene fragment, and one SNP was detected in the 700 bp COX1 gene fragment. In T. britovi, 17 single nucleotide variations (SNVs) were detected in the 5S rDNA gene fragment (among them 16 SNPs), while COX1 sequence analysis revealed the occurrence of 20 SNVs between the sequences tested (among them 19 SNPs). For the majority of T. spiralis isolates the investigated larvae presented uniform haplotypes. In contrast, most of the isolates of T. britovi consisted of larvae of different haplotypes. Geographical analysis showed that each region exhibited different haplotype composition and richness. Warmińsko-Mazurskie and Zachodniopomorskie regions were the richest in haplotypes (15 and 16 haplotypes, respectively). We used heatmaps showing a characteristic pattern for each region graphically. This may allow to differentiate regions based on the occurrence of particular haplotypes. Furthermore, a PCA analysis on the SNP level yielded biplots that show that certain haplotypes/genotypes are associated with (clusters of) regions.
    • Introducing newborn screening for severe combined immunodeficiency (SCID) in the Dutch Neonatal Screening Program.

      Blom, M; Bredius, RGM; Weijman, G; Dekkers, EHBM; Kemper, EA; van den Akker-van Marle, ME; van der Ploeg, CPB; van der Burg, M; Schielen, PCJI (2019-03-12)
    • Inventory of surveillance systems assessing dietary, physical activity and sedentary behaviours in Europe: a DEDIPAC study.

      Bel-Serrat, Silvia; Huybrechts, Inge; Thumann, Barbara F; Hebestreit, Antje; Abuja, Peter M; de Henauw, Stefaan; Dubuisson, Carine; Heuer, Thorsten; Murrin, Celine M; Lazzeri, Giacomo; et al. (2017-08-01)
      There is a need for harmonized public health surveillance systems to monitor regional variations and temporal trends of health behaviours and health outcomes and to align policies, action plans and recommendations in terms of healthy diet and physical (in)activity within Europe. We provide an inventory of currently existing surveillance systems assessing diet, physical activity, and sedentary behaviours in Europe as a tool to assist in the identification of gaps and needs and to contribute to the roadmap for an integrated pan-European surveillance system.
    • An inverse association between the Mediterranean diet and bladder cancer risk: a pooled analysis of 13 cohort studies.

      Witlox, Willem J A; van Osch, Frits H M; Brinkman, Maree; Jochems, Sylvia; Goossens, Maria E; Weiderpass, Elisabete; White, Emily; van den Brandt, Piet A; Giles, Graham G; Milne, Roger L; et al. (2019-02-08)
      The role of diet in bladder carcinogenesis has yet to be established. To date most studies have investigated dietary components individually, rather than as dietary patterns, which may provide stronger evidence for any influence of diet on bladder carcinogenesis. The Mediterranean diet has been associated with many health benefits, but few studies have investigated its association with bladder cancer risk. We investigated the potential association between the Mediterranean diet score (MDS) and risk of developing bladder cancer by pooling 13 prospective cohort studies included in the BLadder cancer Epidemiology and Nutritional Determinants (BLEND) study and applying a Cox regression analysis. Dietary data from 646,222 study participants, including 3639 incident bladder cancer cases, were analysed. We observed an inverse association between Mediterranean diet and bladder cancer risk (HR We found evidence that adherence to the Mediterranean diet was associated with reduced risk of developing bladder cancer, suggesting a positive effect of the diet as a whole and not just one component.
    • Investigation of Rhizospheric Microbial Communities in Wheat, Barley, and Two Rice Varieties at the Seedling Stage

      Lu, Tao; Ke, Mingjing; Peijnenburg, W. J. G. M.; Zhu, Youchao; Zhang, Meng; Sun, Liwei; Fu, Zhengwei; Qian, Haifeng (2018-02-23)
    • IP-10 Kinetics in the First Week of Therapy are Strongly Associated with Bacteriological Confirmation of Tuberculosis Diagnosis in HIV-Infected Patients.

      García-Basteiro, Alberto L; Mambuque, Edson; den Hertog, Alice; Saavedra, Belén; Cuamba, Inocencia; Oliveras, Laura; Blanco, Silvia; Bulo, Helder; Brew, Joe; Cuevas, Luis E; et al. (2017-10-30)
      Simple effective tools to monitor the long treatment of tuberculosis (TB) are lacking. Easily measured host derived biomarkers have been identified but need to be validated in larger studies and different population groups. Here we investigate the early response in IP-10 levels (between day 0 and day 7 of TB therapy) to identify bacteriological status at diagnosis among 127 HIV-infected patients starting TB treatment. All participants were then classified as responding or not responding to treatment blindly using a previously described IP-10 kinetic algorithm. There were 77 bacteriologically confirmed cases and 41 Xpert MTB/RIF® and culture negative cases. Most participants had a measurable decline in IP-10 during the first 7 days of therapy. Bacteriologically confirmed cases were more likely to have high IP-10 levels at D0 and had a steeper decline than clinically diagnosed cases (mean decline difference 2231 pg/dl, 95% CI: 897-3566, p = 0.0013). Bacteriologically confirmed cases were more likely to have a measurable decline in IP-10 at day 7 than clinically diagnosed cases (48/77 (62.3%) vs 13/41 (31.7%), p < 0.001). This study confirms the association between a decrease in IP-10 levels during the first week of treatment and a bacteriological confirmation at diagnosis in a large cohort of HIV positive patients.
    • Is aircraft noise exposure associated with cardiovascular disease and hypertension? Results from a cohort study in Athens, Greece.

      Dimakopoulou, Konstantina; Koutentakis, Konstantinos; Papageorgiou, Ifigeneia; Kasdagli, Maria-Iosifina; Haralabidis, Alexandros S; Sourtzi, Panayota; Samoli, Evangelia; Houthuijs, Danny; Swart, Wim; Hansell, Anna L; et al. (2017-11)
      We followed up, in 2013, the subjects who lived near the Athens International Airport and had participated in the cross-sectional multicountry HYENA study in 2004-2006.
    • Is cumulative fossil energy demand a useful indicator for the environmental performance of products?

      Huijbregts, Mark A J; Rombouts, Linda J A; Hellweg, Stefanie; Frischknecht, Rolf; Hendriks, A Jan; Meent, Dik van de; Ragas, Ad M J; Reijnders, Lucas; Struijs, Jaap (2006-02-01)
      The appropriateness of the fossil Cumulative Energy Demand (CED) as an indicator for the environmental performance of products and processes is explored with a regression analysis between the environmental life-cycle impacts and fossil CEDs of 1218 products, divided into the product categories "energy production", "material production", "transport", and "waste treatment". Our results show that, for all product groups but waste treatment, the fossil CED correlates well with most impact categories, such as global warming, resource depletion, acidification, eutrophication, tropospheric ozone formation, ozone depletion, and human toxicity (explained variance between 46% and 100%). We conclude that the use of fossil fuels is an important driver of several environmental impacts and thereby indicative for many environmental problems. It maytherefore serve as a screening indicatorfor environmental performance. However, the usefulness of fossil CED as a stand-alone indicator for environmental impact is limited by the large uncertainty in the product-specific fossil CED-based impact scores (larger than a factor of 10 for the majority of the impact categories; 95% confidence interval). A major reason for this high uncertainty is nonfossil energy related emissions and land use, such as landfill leachates, radionuclide emissions, and land use in agriculture and forestry.
    • Is current risk assessment of non-genotoxic carcinogens protective?

      Braakhuis, Hedwig M; Slob, Wout; Olthof, Evelyn D; Wolterink, Gerrit; Zwart, Edwin P; Gremmer, Eric R; Rorije, Emiel; van Benthem, Jan; Woutersen, Ruud; van der Laan, Jan Willem; et al. (2018-05-10)
      Non-genotoxic carcinogens (NGTXCs) do not cause direct DNA damage but induce cancer via other mechanisms. In risk assessment of chemicals and pharmaceuticals, carcinogenic risks are determined using carcinogenicity studies in rodents. With the aim to reduce animal testing, REACH legislation states that carcinogenicity studies are only allowed when specific concerns are present; risk assessment of compounds that are potentially carcinogenic by a non-genotoxic mode of action is usually based on subchronic toxicity studies. Health-based guidance values (HBGVs) of NGTXCs may therefore be based on data from carcinogenicity or subchronic toxicity studies depending on the legal framework that applies. HBGVs are usually derived from No-Observed-Adverse-Effect-Levels (NOAELs). Here, we investigate whether current risk assessment of NGTXCs based on NOAELs is protective against cancer. To answer this question, we estimated Benchmark doses (BMDs) for carcinogenicity data of 44 known NGTXCs. These BMDs were compared to the NOAELs derived from the same carcinogenicity studies, as well as to the NOAELs derived from the associated subchronic studies. The results lead to two main conclusions. First, a NOAEL derived from a subchronic study is similar to a NOAEL based on cancer effects from a carcinogenicity study, supporting the current practice in REACH. Second, both the subchronic and cancer NOAELs are, on average, associated with a cancer risk of around 1% in rodents. This implies that for those chemicals that are potentially carcinogenic in humans, current risk assessment of NGTXCs may not be completely protective against cancer. Our results call for a broader discussion within the scientific community, followed by discussions among risk assessors, policy makers, and other stakeholders as to whether or not the potential cancer risk levels that appear to be associated with currently derived HBGVs of NGXTCs are acceptable.
    • Is quality of life impairment associated with chronic diseases dependent on educational level?

      Galenkamp, Henrike; van Oers, Hans A M; Kunst, Anton E; Stronks, Karien (2019-01-18)
      Previous research indicates that quality of life impairment as a result of chronic diseases differs between socioeconomic groups, but the pattern seems to vary between health-related quality of life (HRQOL) outcomes. We tested for a one-item and a multi-item outcome whether associations between diseases and HRQOL varied between educational levels. Data come from Dutch participants of HELIUS (N =4615, aged 18-70). Education was defined as low, middle or high. Myocardial infarction, angina pectoris, hypertension, diabetes, obesity and depressed mood were measured using physical examination and/or self-report. Outcomes were fair/poor self-rated health (SRH) and physical (PCS) and mental (MCS) SF-12 scores. Interaction terms and relative excess risk due to interaction (RERI) were used as measures of additive interaction. SRH and PCS were worst in lower educated participants, whereas MCS was worst in middle educated participants. Out of thirty-six interactions tested, four were statistically significant, with risks of poor HRQOL being both larger and smaller in low vs. high education groups. Obesity was associated with smaller risk of fair/poor SRH in low vs. high educated [RERI=-2.49 (-4.66; -0.33)]. Depressed mood was associated with more [b=-3.34 (-6.14; -0.54)] and hypertension with less reduction in PCS [b=1.23 (0.18; 2.27)] in middle vs. high educated. Depressed mood was highly associated with MCS, but less so in middle vs. high educated [b=4.09 (0.72; 7.47)]. Despite a higher prevalence of diseases in low education groups, if measured in absolute terms, most diseases were not associated with larger impairment of HRQOL in lower vs. higher educated groups, regardless of the outcome measure used.
    • Is there an association between socioeconomic status and immune response to infant and childhood vaccination in the Netherlands?

      van den Boogaard, J; Rots, NY; van der Klis, F; de Melker, HE; Knol, MJ (2020-02-14)
      Introduction Socioeconomic status (SES) is a well-known determinant of health, but its relation with vaccine-induced immunity is less documented. We explored the association between SES and immunoglobulin G (IgG) levels against vaccine-preventable diseases in vaccinated children in the Dutch National Immunization Programme. Methods Data from a population-wide cross-sectional serosurvey in the Netherlands (2006–2007) were used. We compared geometric mean IgG concentrations/titers (GMC/T ratios) against measles, mumps, rubella, Haemophilus influenzae type b (Hib), Neisseria meningococcus type C, diphtheria, tetanus, poliovirus types 1,2,3 and pertussis in children of high versus low SES by linear regression analysis. We included 894 children (0–12 years) at one of two timeframes: 1 month to 1 year, or 1–3 years after vaccination. Mother’s educational level and net household income served as binary indicators of SES. Results Of 58 possible associations of vaccine-induced antibody responses with educational level and 58 with income, 10 (9%) were statistically significant: 2 favouring (that is, with higher IgG levels at) high educational level (for Hib 1 m-1y after vaccination (GMC/T ratio: 2.99, 95%CI: 1.42–6.30) and polio 2 1 m-1y after the 9-year booster dose (1.14, 1.01–1.27)) and 8 favouring low income (polio 1, 2 and 3 1 m-1y after the 11-month booster (0.74, 0.58–0.94; 0.79, 0.64–0.97; 0.72, 0.55–0.95), polio 3 and pertussis 1-3y after the 11-month booster (0.70, 0.56–0.88; pertussis-prn: 0.60, 0.37–0.98; pertussis-ptx: 0.66, 0.47–0.95), mumps and rubella 1-3y after first vaccination (0.73, 0.55–0.97; 0.70, 0.55–0.90), and rubella 1 m-1y after second vaccination (0.83, 0.55–0.90)). After adjustment for multiple testing, none of the differences remained significant. There was no association between SES and proportion of children with protective IgG levels.
    • Isolation of the genome sequence strain Mycobacterium avium 104 from multiple patients over a 17-year period.

      Horan, Kathleen L; Freeman, Robert; Weigel, Kris; Semret, Makeda; Pfaller, Stacy; Covert, Terry C; Soolingen, Dick van; Leão, Sylvia C; Behr, Marcel A; Cangelosi, Gerard A (2006-03-01)
      The genome sequence strain 104 of the opportunistic pathogen Mycobacterium avium was isolated from an adult AIDS patient in Southern California in 1983. Isolates of non-paratuberculosis M. avium from 207 other patients in Southern California and elsewhere were examined for genotypic identity to strain 104. This process was facilitated by the use of a novel two-step approach. In the first step, all 208 strains in the sample were subjected to a high-throughput, large sequence polymorphism (LSP)-based genotyping test, in which DNA from each strain was tested by PCR for the presence or absence of 4 hypervariable genomic regions. Nineteen isolates exhibited an LSP type that resembled that of strain 104. This subset of 19 isolates was then subjected to high-resolution repetitive sequence-based PCR typing, which identified 10 isolates within the subset that were genotypically identical to strain 104. These isolates came from 10 different patients at 5 clinical sites in the western United States, and they were isolated over a 17-year time span. Therefore, the sequenced genome of M. avium strain 104 has been associated with disease in multiple patients in the western United States. Although M. avium is known for its genetic plasticity, these observations also show that strains of the pathogen can be genotypically stable over extended time periods.
    • Isoniazid (INH) mono-resistance and tuberculosis (TB) treatment success: analysis of European surveillance data, 2002 to 2014.

      Karo, Basel; Kohlenberg, Anke; Hollo, Vahur; Duarte, Raquel; Fiebig, Lena; Jackson, Sarah; Kearns, Cathriona; Ködmön, Csaba; Korzeniewska-Kosela, Maria; Papaventsis, Dimitrios; et al. (2019-03-01)
      Isoniazid (INH) is an essential drug for tuberculosis (TB) treatment. Resistance to INH may increase the likelihood of negative treatment outcome. We aimed to determine the impact of INH mono-resistance on TB treatment outcome in the European Union/European Economic Area and to identify risk factors for unsuccessful outcome in cases with INH mono-resistant TB. In this observational study, we retrospectively analysed TB cases that were diagnosed in 2002-14 and included in the European Surveillance System (TESSy). Multilevel logistic regression models were applied to identify risk factors and correct for clustering of cases within countries. A total of 187,370 susceptible and 7,578 INH mono-resistant TB cases from 24 countries were included in the outcome analysis. Treatment was successful in 74.0% of INH mono-resistant and 77.4% of susceptible TB cases. In the final model, treatment success was lower among INH mono-resistant cases (Odds ratio (OR): 0.7; 95% confidence interval (CI): 0.6-0.9; adjusted absolute difference in treatment success: 5.3%). Among INH mono-resistant TB cases, unsuccessful treatment outcome was associated with age above median (OR: 1.3; 95% CI: 1.2-1.5), male sex (OR: 1.3; 95% CI: 1.1-1.4), positive smear microscopy (OR: 1.3; 95% CI: 1.1-1.4), positive HIV status (OR: 3.3; 95% CI: 1.6-6.5) and a prior TB history (OR: 1.8; 95% CI: 1.5-2.2).