• Accessibility of standardized information of a national colorectal cancer screening program for low health literate screening invitees: A mixed method study.

      Fransen, Mirjam P; Dekker, Evelien; Timmermans, Daniëlle R M; Uiters, Ellen; Essink-Bot, Marie-Louise (2017-02)
      To explore the accessibility of standardized printed information materials of the national Dutch colorectal cancer screening program among low health literate screening invitees and to assess the effect of the information on their knowledge about colorectal cancer and the screening program.
    • Acute Otitis Media During Infancy: Parent-reported Incidence and Modifiable Risk Factors.

      Prins-van Ginkel, Annemarijn C; Bruijning-Verhagen, Patricia C J; Uiterwaal, Cuno S P M; van der Ent, Cornelis K; Smit, Henriette A; de Hoog, Marieke L A (2017-03)
      Age at exposure to acute otitis media (AOM) risk factors such as day care attendance, lack of breastfeeding and tobacco smoke is little studied but important for targeting AOM prevention strategies. Moreover, studies are typically restricted to clinically diagnosed AOM, while a significant subset can occur outside the health care system, depending on the country setting. This study aims to determine risk factor exposure and effect of its timing within the first year of life on parent-reported AOM symptom episodes.
    • Added Value of Serum Hormone Measurements in Risk Prediction Models for Breast Cancer for Women Not Using Exogenous Hormones: Results from the EPIC Cohort.

      Hüsing, Anika; Fortner, Renée T; Kühn, Tilman; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Fournier, Agnes; Boeing, Heiner; et al. (2017-08-01)
      Purpose: Circulating hormone concentrations are associated with breast cancer risk, with well-established associations for postmenopausal women. Biomarkers may represent minimally invasive measures to improve risk prediction models.Experimental Design: We evaluated improvements in discrimination gained by adding serum biomarker concentrations to risk estimates derived from risk prediction models developed by Gail and colleagues and Pfeiffer and colleagues using a nested case-control study within the EPIC cohort, including 1,217 breast cancer cases and 1,976 matched controls. Participants were pre- or postmenopausal at blood collection. Circulating sex steroids, prolactin, insulin-like growth factor (IGF) I, IGF-binding protein 3, and sex hormone-binding globulin (SHBG) were evaluated using backward elimination separately in women pre- and postmenopausal at blood collection. Improvement in discrimination was evaluated as the change in concordance statistic (C-statistic) from a modified Gail or Pfeiffer risk score alone versus models, including the biomarkers and risk score. Internal validation with bootstrapping (1,000-fold) was used to adjust for overfitting.Results: Among women postmenopausal at blood collection, estradiol, testosterone, and SHBG were selected into the prediction models. For breast cancer overall, model discrimination after including biomarkers was 5.3 percentage points higher than the modified Gail model alone, and 3.4 percentage points higher than the Pfeiffer model alone, after accounting for overfitting. Discrimination was more markedly improved for estrogen receptor-positive disease (percentage point change in C-statistic: 7.2, Gail; 4.8, Pfeiffer). We observed no improvement in discrimination among women premenopausal at blood collection.Conclusions: Integration of hormone measurements in clinical risk prediction models may represent a strategy to improve breast cancer risk stratification. Clin Cancer Res; 23(15); 4181-9. ©2017 AACR.
    • Adherence to the WCRF/AICR Dietary Recommendations for Cancer Prevention and Risk of Cancer in Elderly from Europe and the United States: A Meta-Analysis within the CHANCES Project.

      Jankovic, Nicole; Geelen, Anouk; Winkels, Renate M; Mwungura, Blaise; Fedirko, Veronika; Jenab, Mazda; Illner, Anne K; Brenner, Hermann; Ordóñez-Mena, José M; Kiefte de Jong, Jessica C; et al. (2017)
      It is unknown whether dietary recommendations for cancer prevention are applicable to the elderly. We analyzed WCRF/AICR recommendations in cohorts of European and U.S. adults ages 60 years and above.
    • Adhering to a national surgical care bundle reduces the risk of surgical site infections.

      Koek, Mayke B G; Hopmans, Titia E M; Soetens, Loes C; Wille, Jan C; Geerlings, Suzanne E; Vos, Margreet C; van Benthem, Birgit H B; de Greeff, Sabine C (2017)
      In 2008, a bundle of care to prevent Surgical Site Infections (SSIs) was introduced in the Netherlands. The bundle consisted of four elements: antibiotic prophylaxis according to local guidelines, no hair removal, normothermia and 'hygiene discipline' in the operating room (i.e. number of door movements). Dutch hospitals were advised to implement the bundle and to measure the outcome. This study's goal was to assess how effective the bundle was in reducing SSI risk.
    • Age-specific Incidence and Prevalence of Keratoconus: A Nationwide Registration Study.

      Godefrooij, Daniel A; de Wit, G Ardine; Uiterwaal, Cuno S; Imhof, Saskia M; Wisse, Robert P L (2017-03)
      To determine the age-specific incidence and prevalence of keratoconus in the modern era of diagnostics.
    • Air Pollution from Livestock Farms Is Associated with Airway Obstruction in Neighboring Residents.

      Borlée, Floor; Yzermans, C Joris; Aalders, Bernadette; Rooijackers, Jos; Krop, Esmeralda; Maassen, Catharina B M; Schellevis, François; Brunekreef, Bert; Heederik, Dick; Smit, Lidwien A M (2017-11-01)
      Livestock farm emissions may not only affect respiratory health of farmers but also of neighboring residents.
    • Alcohol consumption and risk of urothelial cell bladder cancer in the European prospective investigation into cancer and nutrition cohort.

      Botteri, E; Ferrari, P; Roswall, N; Tjønneland, A; Hjartåker, A; Huerta, J M; Fortner, R T; Trichopoulou, A; Karakatsani, A; La Vecchia, C; et al. (2017-11-15)
      Findings on the association between alcohol consumption and bladder cancer are inconsistent. We investigated that association in the European Prospective Investigation into Cancer and Nutrition cohort. We included 476,160 individuals mostly aged 35-70 years, enrolled in ten countries and followed for 13.9 years on average. Hazard ratios (HR) for developing urothelial cell carcinoma (UCC; 1,802 incident cases) were calculated using Cox proportional hazards models. Alcohol consumption at baseline and over the life course was analyzed, as well as different types of beverages (beer, wine, spirits). Baseline alcohol intake was associated with a statistically nonsignificant increased risk of UCC (HR 1.03; 95% confidence interval (CI) 1.00-1.06 for each additional 12 g/day). HR in smokers was 1.04 (95% CI 1.01-1.07). Men reporting high baseline intakes of alcohol (>96 g/day) had an increased risk of UCC (HR 1.57; 95% CI 1.03-2.40) compared to those reporting moderate intakes (<6 g/day), but no dose-response relationship emerged. In men, an increased risk of aggressive forms of UCC was observed even at lower doses (>6 to 24 g/day). Average lifelong alcohol intake was not associated with the risk of UCC, however intakes of spirits > 24 g/day were associated with an increased risk of UCC in men (1.38; 95% CI 1.01-1.91) and smokers (1.39; 95% CI 1.01-1.92), compared to moderate intakes. We found no association between alcohol and UCC in women and never smokers. In conclusion, we observed some associations between alcohol and UCC in men and in smokers, possibly because of residual confounding by tobacco smoking.
    • Allergic contact cheilitis caused by olaflur in toothpaste.

      de Groot, Anton; Tupker, Ron; Hissink, Diny; Woutersen, Marjolijn (2017-01)
    • Ambient air pollution and primary liver cancer incidence in four European cohorts within the ESCAPE project.

      Pedersen, Marie; Andersen, Zorana J; Stafoggia, Massimo; Weinmayr, Gudrun; Galassi, Claudia; Sørensen, Mette; Eriksen, Kirsten T; Tjønneland, Anne; Loft, Steffen; Jaensch, Andrea; et al. (2017)
      Tobacco smoke exposure increases the risk of cancer in the liver, but little is known about the possible risk associated with exposure to ambient air pollution.
    • Anti-Müllerian Hormone Trajectories Are Associated With Cardiovascular Disease in Women: Results From the Doetinchem Cohort Study.

      de Kat, Annelien C; Verschuren, W Monique; Eijkemans, Marinus J C; Broekmans, Frank J M; van der Schouw, Yvonne T (2017-02-07)
      Earlier age at menopause is widely considered to be associated with an increased risk of cardiovascular disease. However, the underlying mechanisms of this relationship remain undetermined. Indications suggest that anti-Müllerian hormone (AMH), an ovarian reserve marker, plays a physiological role outside of the reproductive system. Therefore, we investigated whether longitudinal AMH decline trajectories are associated with an increased risk of cardiovascular disease (CVD) occurrence.
    • Antiviral Activity of Pocapavir in a Randomized, Blinded, Placebo-Controlled Human Oral Poliovirus Vaccine Challenge Model.

      Collett, Marc S; Hincks, Jeffrey R; Benschop, Kimberley; Duizer, Erwin; van der Avoort, Harrie; Rhoden, Eric; Liu, Hongmei; Oberste, M Steven; McKinlay, Mark A; Hartford, Marianne (2017-02-01)
      Immunodeficient individuals who excrete vaccine-derived polioviruses threaten polio eradication. Antivirals address this threat.
    • Antiviral susceptibility profile of influenza A viruses; keep an eye on immunocompromised patients under prolonged treatment.

      Kossyvakis, A; Mentis, A-F A; Tryfinopoulou, K; Pogka, V; Kalliaropoulos, A; Antalis, E; Lytras, T; Meijer, A; Tsiodras, S; Karakitsos, P; et al. (2017-02)
      There was an increase in severe and fatal influenza cases in Greece during the 2011-2015 post-pandemic period. To investigate causality, we determined neuraminidase (NA) inhibitor susceptibility and resistance-conferring NA and hemagglutinin (HA) mutations in circulating influenza type A viruses during the pandemic (2009-2010) and post-pandemic periods in Greece. One hundred thirty-four influenza A(H1N1)pdm09 and 95 influenza A(H3N2) viruses submitted to the National Influenza Reference Laboratory of Southern Greece were tested for susceptibility to oseltamivir and zanamivir. Antiviral resistance was assessed by neuraminidase sequence analysis, as well as the fluorescence-based 50 % inhibitory concentration (IC50) method. Five influenza A(H1N1)pdm09 viruses (2.2 %) showed significantly reduced inhibition by oseltamivir (average IC50 300.60nM vs. 1.19nM) by Gaussian kernel density plot analysis. These viruses were isolated from immunocompromised patients and harbored the H275Y oseltamivir resistance-conferring NA substitution. All A(H1N1)pdm09 viruses were zanamivir-susceptible, and all A(H3N2) viruses were susceptible to both drugs. Oseltamivir-resistant viruses did not form a distinct cluster by phylogenetic analysis. Permissive mutations were detected in immunogenic and non immunogenic NA regions of both oseltamivir- resistant and susceptible viruses in the post-pandemic seasons. Several amino acid substitutions in the HA1 domain of the HA gene of post-pandemic viruses were identified. This study indicated low resistance to NAIs among tested influenza viruses. Antiviral resistance emerged only in immunocompromised patients under long-term oseltamivir treatment. Sequential sample testing in this vulnerable group of patients is recommended to characterise resistance or reinfection and viral evolution.
    • Appropriate antibiotic use reduces length of hospital stay.

      van den Bosch, Caroline M A; Hulscher, Marlies E J L; Akkermans, Reinier P; Wille, Jan; Geerlings, Suzanne E; Prins, Jan M (2017)
      To define appropriate antibiotic use in hospitalized adults treated for a bacterial infection, we previously developed and validated a set of six generic quality indicators (QIs) covering all steps in the process of antibiotic use. We assessed the association between appropriate antibiotic use, defined by these QIs, and length of hospital stay (LOS).
    • Assessment of Fecal Exposure Pathways in Low-Income Urban Neighborhoods in Accra, Ghana: Rationale, Design, Methods, and Key Findings of the SaniPath Study.

      Robb, Katharine; Null, Clair; Teunis, Peter; Yakubu, Habib; Armah, George; Moe, Christine L (2017-10)
      Rapid urbanization has contributed to an urban sanitation crisis in low-income countries. Residents in low-income, urban neighborhoods often have poor sanitation infrastructure and services and may experience frequent exposure to fecal contamination through a range of pathways. There are little data to prioritize strategies to decrease exposure to fecal contamination in these complex and highly contaminated environments, and public health priorities are rarely considered when planning urban sanitation investments. The SaniPath Study addresses this need by characterizing pathways of exposure to fecal contamination. Over a 16 month period, an in-depth, interdisciplinary exposure assessment was conducted in both public and private domains of four neighborhoods in Accra, Ghana. Microbiological analyses of environmental samples and behavioral data collection techniques were used to quantify fecal contamination in the environment and characterize the behaviors of adults and children associated with exposure to fecal contamination. Environmental samples (n = 1,855) were collected and analyzed for fecal indicators and enteric pathogens. A household survey with 800 respondents and over 500 hours of structured observation of young children were conducted. Approximately 25% of environmental samples were collected in conjunction with structured observations (n = 441 samples). The results of the study highlight widespread and often high levels of fecal contamination in both public and private domains and the food supply. The dominant fecal exposure pathway for young children in the household was through consumption of uncooked produce. The SaniPath Study provides critical information on exposure to fecal contamination in low-income, urban environments and ultimately can inform investments and policies to reduce these public health risks.
    • Associations between lifestyle and air pollution exposure: Potential for confounding in large administrative data cohorts.

      Strak, Maciej; Janssen, Nicole; Beelen, Rob; Schmitz, Oliver; Karssenberg, Derek; Houthuijs, Danny; van den Brink, Carolien; Dijst, Martin; Brunekreef, Bert; Hoek, Gerard (2017)
      Cohorts based on administrative data have size advantages over individual cohorts in investigating air pollution risks, but often lack in-depth information on individual risk factors related to lifestyle. If there is a correlation between lifestyle and air pollution, omitted lifestyle variables may result in biased air pollution risk estimates. Correlations between lifestyle and air pollution can be induced by socio-economic status affecting both lifestyle and air pollution exposure.
    • Associations between lifestyle factors and an unhealthy diet.

      Fransen, Heidi P; Boer, Jolanda M A; Beulens, Joline W J; de Wit, G Ardine; Bueno-de-Mesquita, H Bas; Hoekstra, Jeljer; May, Anne M; Peeters, Petra H M (2017)
      : Unhealthy dietary patterns have been associated with other unhealthy lifestyle factors such as smoking and physical inactivity. Whether these associations are similar in high- and low-educated individuals is currently unknown.
    • Baseline incidence of intussusception in early childhood before rotavirus vaccine introduction, the Netherlands, January 2008 to December 2012.

      Gadroen, Kartini; Kemmeren, Jeanet M; Bruijning-Verhagen, Patricia Cj; Straus, Sabine Mjm; Weibel, Daniel; de Melker, Hester E; Sturkenboom, Miriam Cjm (2017-06-22)
      Intussusception is a rare, potentially life-threatening condition in early childhood. It gained attention due to an unexpected association with the first rotavirus vaccine, RotaShield, which was subsequently withdrawn from the market. Across Europe, broad variations in intussusception incidence rates have been reported. This study provides a first estimate of intussusception incidence in young children in the Netherlands from 1 January 2008 to 31 December 2012, which could be used for future rotavirus safety monitoring. Our estimates are based on two different sources: electronic medical records from the primary healthcare database (IPCI), as well as administrative data from the Dutch hospital register (LBZ). The results from our study indicate a low rate of intussusception. Overall incidence rate in children < 36 months of age was 21.2 per 100,000 person-years (95% confidence interval (CI): 12.5-34.3) based on primary healthcare data and 22.6 per 100,000 person-years (95% CI: 20.9-24.4) based on hospital administrative data. The estimates suggest the upper and lower bound of the expected number of cases.
    • Changes in LXR signaling influence early-pregnancy lipogenesis and protect against dysregulated fetoplacental lipid homeostasis.

      Nikolova, Vanya; Papacleovoulou, Georgia; Bellafante, Elena; Borges Manna, Luiza; Jansen, Eugene; Baron, Silvère; Abu-Hayyeh, Shadi; Parker, Malcolm; Williamson, Catherine (2017-10-01)
      Human pregnancy is associated with enhanced de novo lipogenesis in the early stages followed by hyperlipidemia during advanced gestation. Liver X receptors (LXRs) are oxysterol-activated nuclear receptors that stimulate de novo lipogenesis and also promote the efflux of cholesterol from extrahepatic tissues followed by its transport back to the liver for biliary excretion. Although LXR is recognized as a master regulator of triglyceride and cholesterol homeostasis, it is unknown whether it facilitates the gestational adaptations in lipid metabolism. To address this question, biochemical profiling, protein quantification, and gene expression studies were used, and gestational metabolic changes in T0901317-treated wild-type mice and Lxrab-/- mutants were investigated. Here, we show that altered LXR signaling contributes to the enhanced lipogenesis in early pregnancy by increasing the expression of hepatic Fas and stearoyl-CoA desaturase 1 (Scd1). Both the pharmacological activation of LXR with T0901317 and the genetic ablation of its two isoforms disrupted the increase in hepatic fatty acid biosynthesis and the development of hypertriglyceridemia during early gestation. We also demonstrate that absence of LXR enhances maternal white adipose tissue lipolysis, causing abnormal accumulation of triglycerides, cholesterol, and free fatty acids in the fetal liver. Together, these data identify LXR as an important factor in early-pregnancy lipogenesis that is also necessary to protect against abnormalities in fetoplacental lipid homeostasis.
    • Characterizing Adult Sleep Behavior Over 20 Years-The Population-Based Doetinchem Cohort Study.

      Zomers, Margot L; Hulsegge, Gerben; van Oostrom, Sandra H; Proper, Karin I; Verschuren, W M Monique; Picavet, H Susan J (2017-07-01)
      To describe sleep duration patterns of adults over a 20-year period; to compare sociodemographic, lifestyle, and health characteristics across these patterns; and to relate the patterns to sleep quality.