• Coffee Drinking and Mortality in 10 European Countries: A Multinational Cohort Study.

      Gunter, Marc J; Murphy, Neil; Cross, Amanda J; Dossus, Laure; Dartois, Laureen; Fagherazzi, Guy; Kaaks, Rudolf; Kühn, Tilman; Boeing, Heiner; Aleksandrova, Krasimira; et al. (2017-08-15)
      The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear.
    • A combination of plasma phospholipid fatty acids and its association with incidence of type 2 diabetes: The EPIC-InterAct case-cohort study.

      Imamura, Fumiaki; Sharp, Stephen J; Koulman, Albert; Schulze, Matthias B; Kröger, Janine; Griffin, Julian L; Huerta, José M; Guevara, Marcela; Sluijs, Ivonne; Agudo, Antonio; et al. (2017-10)
      Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated.
    • Comparing viral load metrics and evaluating their use for HIV surveillance.

      Bolijn, Renee; Op de Coul, Eline L M; van Sighem, Ard; Blok, Willem L; Kretzschmar, Mirjam E; Heijne, Janneke C M (2017-08)
      To investigate the value of in-care viral load (ICVL) and other viral load (VL) metrics for HIV surveillance by comparing time trends and associations with numbers of new HIV diagnoses.
    • Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe.

      Freisling, Heinz; Arnold, Melina; Soerjomataram, Isabelle; O'Doherty, Mark George; Ordóñez-Mena, José Manuel; Bamia, Christina; Kampman, Ellen; Leitzmann, Michael; Romieu, Isabelle; Kee, Frank; et al. (2017-05-23)
      We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to-hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence.
    • Comparison of mucosal lining fluid sampling methods and influenza-specific IgA detection assays for use in human studies of influenza immunity.

      de Silva, Thushan I; Gould, Victoria; Mohammed, Nuredin I; Cope, Alethea; Meijer, Adam; Zutt, Ilse; Reimerink, Johan; Kampmann, Beate; Hoschler, Katja; Zambon, Maria; et al. (2017-10)
      We need greater understanding of the mechanisms underlying protection against influenza virus to develop more effective vaccines. To do this, we need better, more reproducible methods of sampling the nasal mucosa. The aim of the current study was to compare levels of influenza virus A subtype-specific IgA collected using three different methods of nasal sampling. Samples were collected from healthy adult volunteers before and after LAIV immunization by nasal wash, flocked swabs and Synthetic Absorptive Matrix (SAM) strips. Influenza A virus subtype-specific IgA levels were measured by haemagglutinin binding ELISA or haemagglutinin binding microarray and the functional response was assessed by microneutralization. Nasosorption using SAM strips lead to the recovery of a more concentrated sample of material, with a significantly higher level of total and influenza H1-specific IgA. However, an equivalent percentage of specific IgA was observed with all sampling methods when normalized to the total IgA. Responses measured using a recently developed antibody microarray platform, which allows evaluation of binding to multiple influenza strains simultaneously with small sample volumes, were compared to ELISA. There was a good correlation between ELISA and microarray values. Material recovered from SAM strips was weakly neutralizing when used in an in vitro assay, with a modest correlation between the level of IgA measured by ELISA and neutralization, but a greater correlation between microarray-measured IgA and neutralizing activity. In conclusion we have tested three different methods of nasal sampling and show that flocked swabs and novel SAM strips are appropriate alternatives to traditional nasal washes for assessment of mucosal influenza humoral immunity.
    • Consumption of Fish Is Not Associated with Risk of Differentiated Thyroid Carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.

      Zamora-Ros, Raul; Castañeda, Jazmín; Rinaldi, Sabina; Cayssials, Valerie; Slimani, Nadia; Weiderpass, Elisabete; Tsilidis, Konstantinos K; Boutron-Ruault, Marie-Christine; Overvad, Kim; Eriksen, Anne K; et al. (2017)
      Background: Differentiated thyroid cancer (TC) is the most common endocrine cancer. Fish can be an important source of iodine and other micronutrients and contaminants that may affect the thyroid gland and TC risk.Objective: We prospectively evaluated the relations between the consumption of total fish and different fish types and shellfish and TC risk in the EPIC (European Prospective Investigation into Cancer and Nutrition) study.Methods: EPIC is a cohort of >500,000 men and women, mostly aged 35-70 y, who were recruited in 10 European countries. After a mean follow-up of 14 y, 748 primary differentiated TC cases were diagnosed; 666 were in women and 601 were papillary TC. Data on intakes of lean fish, fatty fish, fish products, and shellfish were collected by using country-specific validated dietary questionnaires at recruitment. Multivariable Cox regression was used to calculate HRs and 95% CIs adjusted for many potential confounders, including dietary and nondietary factors.Results: No significant association was observed between total fish consumption and differentiated TC risk for the highest compared with the lowest quartile (HR: 1.03; 95% CI: 0.81, 1.32; P-trend = 0.67). Likewise, no significant association was observed with the intake of any specific type of fish, fish product, or shellfish. No significant heterogeneity was found by TC subtype (papillary or follicular tumors), by sex, or between countries with low and high TC incidence.Conclusion: This large study shows that the intake of fish and shellfish was not associated with differentiated TC risk in Europe, a region in which iodine deficiency or excess is rare.
    • Consumption of fruits, vegetables and fruit juices and differentiated thyroid carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

      Zamora-Ros, Raul; Béraud, Virginie; Franceschi, Silvia; Cayssials, Valerie; Tsilidis, Konstantinos K; Boutron-Ruault, Marie-Christine; Weiderpass, Elisabete; Overvad, Kim; Tjønneland, Anne; Eriksen, Anne K; et al. (2018-02-01)
      Fruit and vegetable (F&V) intake is considered as probably protective against overall cancer risk, but results in previous studies are not consistent for thyroid cancer (TC). The purpose of this study is to examine the association between the consumption of fruits, vegetables, fruit juices and differentiated thyroid cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The EPIC study is a cohort including over half a million participants, recruited between 1991 and 2000. During a mean follow-up of 14 years, 748 incident first primary differentiated TC cases were identified. F&V and fruit juice intakes were assessed through validated country-specific dietary questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models adjusted for potential confounding factors. Comparing the highest versus lowest quartile of intake, differentiated TC risk was not associated with intakes of total F&V (HR: 0.89; 95% CI: 0.68-1.15; p-trend = 0.44), vegetables (HR: 0.89; 95% CI: 0.69-1.14; p-trend = 0.56), or fruit (HR: 1.00; 95% CI: 0.79-1.26; p-trend = 0.64). No significant association was observed with any individual type of vegetable or fruit. However, there was a positive borderline trend with fruit juice intake (HR: 1.23; 95% CI: 0.98-1.53; p-trend = 0.06). This study did not find any significant association between F&V intakes and differentiated TC risk; however a positive trend with fruit juice intake was observed, possibly related to its high sugar content.
    • Consumption of whole grains, fruit and vegetables is not associated with indices of renal function in the population-based longitudinal Doetinchem study.

      Herber-Gast, Gerrie-Cor M; Boersma, Marijke; Verschuren, W M Monique; Stehouwer, Coen D A; Gansevoort, Ron T; Bakker, Stephan J L; Spijkerman, Annemieke M W (2017-09)
      Emerging evidence suggests that diet and renal function are related. Little is known, however, about the association of consumption of whole grains, fruit and vegetables with urinary albumin:creatinine ratio (ACR) and changes in estimated glomerular filtration rate (eGFR). We investigated this in a population-based cohort aged 26-65 years. Data were from 3787 participants from the Doetinchem cohort study, who were examined ≥3 times, 5 years apart. Consumption of food groups was assessed at each round with a validated FFQ. GFR was estimated at each round from routinely measured cystatin C and creatinine using the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation. ACR was measured at the last round. Generalised estimated equation models were performed to examine associations with changes in eGFR. Linear regression was used to examine associations with ACR. Adjustments were made for covariates related to lifestyle, biological factors and diet. Mean baseline eGFR was 104·5 (sd 13·7) and mean annual decline was -0·95 (sd 0·67) ml/min per 1·73 m2 over a 15-year follow-up. A trend was observed towards slightly less annual decline in eGFR among those with higher consumption of whole grains (P=0·06). This association, however, was attenuated and no longer significant in multivariate models (P=0·29). Consumption of fruit and vegetables was not associated with changes in eGFR and urinary ACR. In conclusion, consumption of whole grains, fruit and vegetables is not associated with changes in eGFR and mean ACR. As this was the first longitudinal study into this association in the general population, and as results are only partially in line with related studies, further research is recommended.
    • Coxiella burnetii (Q fever) prevalence in associated populations of humans and small ruminants in The Gambia.

      Bok, Jeroen; Hogerwerf, Lenny; Germeraad, Eveline A; Roest, Hendrik I J; Faye-Joof, Tisbeh; Jeng, Momodou; Nwakanma, Davis; Secka, Arss; Stegeman, Arjan; Goossens, Bart; et al. (2017)
      To simultaneously estimate the prevalence of antibodies against Coxiella burnetii (Q fever) among adults and small ruminants, and C. burnetii shedding prevalence among small ruminants in households in the Kiang West district of The Gambia, and to assess associated risk factors.
    • Current prevalence of chronic hepatitis B and C virus infection in the general population, blood donors and pregnant women in the EU/EEA: a systematic review.

      Hofstraat, S H I; Falla, A M; Duffell, E F; Hahné, S J M; Amato-Gauci, A J; Veldhuijzen, I K; Tavoschi, L (2017)
      This systematic review aimed at estimating chronic hepatitis B (HBV) and C virus (HCV) prevalence in the European Union (EU) and Economic Area (EEA) countries in the general population, blood donors and pregnant women. We searched PubMed©, Embase© and Cochrane Library databases for reports on HBV and HCV prevalence in the general population and pregnant women in EU/EEA countries published between 2005 and 2015. Council of Europe data were used for HBV and HCV blood donor prevalence. HBV general population estimates were available for 13 countries, ranging from 0·1% to 4·4%. HCV general population estimates were available for 13 countries, ranging from 0·1% to 5·9%. Based on general population and blood donor estimates, the overall HBV prevalence in the EU/EEA is estimated to be 0·9% (95% CI 0·7-1·2), corresponding to almost 4·7 million HBsAg-positive cases; and the overall HCV prevalence to be 1·1% (95% CI 0·9-1·4), equalling 5·6 million anti-HCV-positive cases. We found wide variation in HCV and HBV prevalence across EU/EEA countries for which estimates were available, as well as variability between groups often considered a proxy for the general population. Prevalence estimates are essential to inform policymaking and public health practice. Comparing to other regions globally, HBV and HCV prevalence in the EU/EEA is low.
    • Dietary restriction but not angiotensin II type 1 receptor blockade improves DNA damage-related vasodilator dysfunction in rapidly aging Ercc1Δ/- mice.

      Wu, Haiyan; van Thiel, Bibi S; Bautista-Niño, Paula K; Reiling, Erwin; Durik, Matej; Leijten, Frank P J; Ridwan, Yanto; Brandt, Renata M C; van Steeg, Harry; Dollé, Martijn E T; et al. (2017-08-01)
      DNA damage is an important contributor to endothelial dysfunction and age-related vascular disease. Recently, we demonstrated in a DNA repair-deficient, prematurely aging mouse model (Ercc1Δ/- mice) that dietary restriction (DR) strongly increases life- and health span, including ameliorating endothelial dysfunction, by preserving genomic integrity. In this mouse mutant displaying prominent accelerated, age-dependent endothelial dysfunction we investigated the signaling pathways involved in improved endothelium-mediated vasodilation by DR, and explore the potential role of the renin-angiotensin system (RAS). Ercc1Δ/- mice showed increased blood pressure and decreased aortic relaxations to acetylcholine (ACh) in organ bath experiments. Nitric oxide (NO) signaling and phospho-Ser1177-eNOS were compromised in Ercc1Δ/- DR improved relaxations by increasing prostaglandin-mediated responses. Increase of cyclo-oxygenase 2 and decrease of phosphodiesterase 4B were identified as potential mechanisms. DR also prevented loss of NO signaling in vascular smooth muscle cells and normalized angiotensin II (Ang II) vasoconstrictions, which were increased in Ercc1Δ/- mice. Ercc1Δ/- mutants showed a loss of Ang II type 2 receptor-mediated counter-regulation of Ang II type 1 receptor-induced vasoconstrictions. Chronic losartan treatment effectively decreased blood pressure, but did not improve endothelium-dependent relaxations. This result might relate to the aging-associated loss of treatment efficacy of RAS blockade with respect to endothelial function improvement. In summary, DR effectively prevents endothelium-dependent vasodilator dysfunction by augmenting prostaglandin-mediated responses, whereas chronic Ang II type 1 receptor blockade is ineffective.
    • Distribution of serotypes and patterns of antimicrobial resistance among commensal Streptococcus pneumoniae in nine European countries.

      Yahiaoui, Rachid Y; Bootsma, Hester J; den Heijer, Casper D J; Pluister, Gerlinde N; John Paget, W; Spreeuwenberg, Peter; Trzcinski, Krzysztof; Stobberingh, Ellen E (2018-08-29)
      Streptococcus pneumoniae is a commensal of the human upper respiratory tract and a major cause of morbidity and mortality worldwide. This paper presents the distribution of serotypes and antimicrobial resistance in commensal S. pneumoniae strains cultured from healthy carriers older than four years of age in nine European countries.
    • Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation.

      Campa, Daniele; Pastore, Manuela; Capurso, Gabriele; Hackert, Thilo; Di Leo, Milena; Izbicki, Jakob R; Khaw, Kay-Tee; Gioffreda, Domenica; Kupcinskas, Juozas; Pasquali, Claudio; et al. (2018-01-15)
      Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous  = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous  = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10-6 ) and MORC4-rs 12837024 (ORhomozygous  = 2.07 (1.55-2.77, ptrend  = 0.7 × 10-11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants.
    • Does a better adherence to dietary guidelines reduce mortality risk and environmental impact in the Dutch sub-cohort of the European Prospective Investigation into Cancer and Nutrition?

      Biesbroek, Sander; Verschuren, W M Monique; Boer, Jolanda M A; van de Kamp, Mirjam E; van der Schouw, Yvonne T; Geelen, Anouk; Looman, Moniek; Temme, Elisabeth H M (2017-07)
      Guidelines for a healthy diet aim to decrease the risk of chronic diseases. It is unclear as to what extent a healthy diet is also an environmentally friendly diet. In the Dutch sub-cohort of the European Prospective Investigation into Cancer and Nutrition, the diet was assessed with a 178-item FFQ of 40 011 participants aged 20-70 years between 1993 and 1997. The WHO's Healthy Diet Indicator (HDI), the Dietary Approaches to Stop Hypertension (DASH) score and the Dutch Healthy Diet index 2015 (DHD15-index) were investigated in relation to greenhouse gas (GHG) emissions, land use and all-cause mortality risk. GHG emissions were associated with HDI scores (-3·7 % per sd increase (95 % CI -3·4, -4·0) for men and -1·9 % (95 % CI -0·4, -3·4) for women), with DASH scores in women only (1·1 % per sd increase, 95 % CI 0·9, 1·3) and with DHD15-index scores (-2·5 % per sd increase (95 % CI -2·2, -2·8) for men and -2·0 % (95 % CI -1·9, -2·2) for women). For all indices, higher scores were associated with less land use (ranging from -1·3 to -3·1 %). Mortality risk decreased with increasing scores for all indices. Per sd increase of the indices, hazard ratios for mortality ranged from 0·88 (95 % CI 0·82, 0·95) to 0·96 (95 % CI 0·92, 0·99). Our results showed that adhering to the WHO and Dutch dietary guidelines will lower the risk of all-cause mortality and moderately lower the environmental impact. The DASH diet was associated with lower mortality and land use, but because of high dairy product consumption in the Netherlands it was also associated with higher GHG emissions.
    • Does the Health Impact of Exposure to Neighbourhood Green Space Differ between Population Groups? An Explorative Study in Four European Cities.

      Ruijsbroek, Annemarie; Droomers, Mariël; Kruize, Hanneke; van Kempen, Elise; Gidlow, Christopher J; Hurst, Gemma; Andrusaityte, Sandra; Nieuwenhuijsen, Mark J; Maas, Jolanda; Hardyns, Wim; et al. (2017-06-08)
      It has been suggested that certain residents, such as those with a low socioeconomic status, the elderly, and women, may benefit more from the presence of neighbourhood green space than others. We tested this hypothesis for age, gender, educational level, and employment status in four European cities. Data were collected in Barcelona (Spain; n = 1002), Kaunas (Lithuania; n = 989), Doetinchem (The Netherlands; n = 847), and Stoke-on-Trent (UK; n = 933) as part of the EU-funded PHENOTYPE project. Surveys were used to measure mental and general health, individual characteristics, and perceived neighbourhood green space. Additionally, we used audit data about neighbourhood green space. In Barcelona, there were positive associations between neighbourhood green space and general health among low-educated residents. In the other cities and for the other population groups, there was little evidence that the association between health and neighbourhood green space differed between population groups. Overall, our study does not support the assumption that the elderly, women, and residents who are not employed full-time benefit more from neighbourhood green space than others. Only in the highly urbanised city of Barcelona did the low-educated group benefit from neighbourhood green spaces. Perhaps neighbourhood green spaces are more important for the health of low-educated residents in particularly highly urbanised areas.
    • Effectiveness of Early Measles, Mumps, and Rubella Vaccination Among 6-14-Month-Old Infants During an Epidemic in the Netherlands: An Observational Cohort Study.

      Woudenberg, Tom; van der Maas, Nicoline A T; Knol, Mirjam J; de Melker, Hester; van Binnendijk, Rob S; Hahné, Susan J M (2017-04-15)
      Routinely, the first measles, mumps, and rubella (MMR) vaccine dose is given at 14 months of age in the Netherlands. However, during a measles epidemic in 2013-2014, MMR vaccination was also offered to 6-14-month-olds in municipalities with <90% MMR vaccination coverage. We studied the effectiveness of the early MMR vaccination schedule.
    • Elevated Immune Response Among Children 4 Years of Age With Pronounced Local Adverse Events After the Fifth Diphtheria, Tetanus, Acellular Pertussis Vaccination.

      van der Lee, Saskia; Kemmeren, Jeanet M; de Rond, Lia G H; Öztürk, Kemal; Westerhof, Anneke; de Melker, Hester E; Sanders, Elisabeth A M; Berbers, Guy A M; van der Maas, Nicoline A T; Rümke, Hans C; et al. (2017-09)
      In the Netherlands, acellular pertussis vaccines replaced the more reactogenic whole-cell pertussis vaccines. This replacement in the primary immunization schedule of infants coincided with a significant increase in pronounced local adverse events (AEs) in 4 years old children shortly after the administration of a fifth diphtheria, tetanus, acellular pertussis and inactivated polio (DTaP-IPV) vaccine. The objective of this study was to investigate possible differences in vaccine antigen-specific immune responses between children with and without a pronounced local AE after the fifth DTaP-IPV vaccination.
    • Estimation of age-specific rates of reactivation and immune boosting of the varicella zoster virus.

      Marinelli, Isabella; van Lier, Alies; de Melker, Hester; Pugliese, Andrea; van Boven, Michiel (2017)
      Studies into the impact of vaccination against the varicella zoster virus (VZV) have increasingly focused on herpes zoster (HZ), which is believed to be increasing in vaccinated populations with decreasing infection pressure. This idea can be traced back to Hope-Simpson's hypothesis, in which a person's immune status determines the likelihood that he/she will develop HZ. Immunity decreases over time, and can be boosted by contact with a person experiencing varicella (exogenous boosting) or by a reactivation attempt of the virus (endogenous boosting). Here we use transmission models to estimate age-specific rates of reactivation and immune boosting, exogenous as well as endogenous, using zoster incidence data from the Netherlands (2002-2011, n=7026). The boosting and reactivation rates are estimated with splines, enabling these quantities to be optimally informed by the data. The analyses show that models with high levels of exogenous boosting and estimated or zero endogenous boosting, constant rate of loss of immunity, and reactivation rate increasing with age (to more than 5% per year in the elderly) give the best fit to the data. Estimates of the rates of immune boosting and reactivation are strongly correlated. This has important implications as these parameters determine the fraction of the population with waned immunity. We conclude that independent evidence on rates of immune boosting and reactivation in persons with waned immunity are needed to robustly predict the impact of varicella vaccination on the incidence of HZ.
    • Excess all-cause and influenza-attributable mortality in Europe, December 2016 to February 2017.

      Vestergaard, Lasse S; Nielsen, Jens; Krause, Tyra G; Espenhain, Laura; Tersago, Katrien; Bustos Sierra, Natalia; Denissov, Gleb; Innos, Kaire; Virtanen, Mikko J; Fouillet, Anne; et al. (2017-04-06)
      Since December 2016, excess all-cause mortality was observed in many European countries, especially among people aged ≥ 65 years. We estimated all-cause and influenza-attributable mortality in 19 European countries/regions. Excess mortality was primarily explained by circulation of influenza virus A(H3N2). Cold weather snaps contributed in some countries. The pattern was similar to the last major influenza A(H3N2) season in 2014/15 in Europe, although starting earlier in line with the early influenza season start.
    • Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study.

      Fedirko, Veronika; Tran, Hao Quang; Gewirtz, Andrew T; Stepien, Magdalena; Trichopoulou, Antonia; Aleksandrova, Krasimira; Olsen, Anja; Tjønneland, Anne; Overvad, Kim; Carbonnel, Franck; et al. (2017-04-04)
      Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking.