• Dietary folate intake and pancreatic cancer risk: Results from the European Prospective Investigation into Cancer and Nutrition.

      Park, Jin Young; Bueno-de-Mesquita, H Bas; Ferrari, Pietro; Weiderpass, Elisabete; de Batlle, Jordi; Tjønneland, Anne; Kyro, Cecilie; Rebours, Vinciane; Boutron-Ruault, Marie-Christine; Mancini, Francesca Romana; et al. (2018-09-04)
      Pancreatic cancer (PC) has an exceptionally low survival rate and primary prevention strategies are limited. Folate plays an important role in one-carbon metabolism and has been associated with the risk of several cancers, but not consistently with PC risk. We aimed to investigate the association between dietary folate intake and PC risk, using the standardised folate database across 10 European countries. A total of 477,206 participants were followed up for 11 years, during which 865 incident primary PC cases were recorded. Folate intake was energy-adjusted using the residual method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. In multivariable analyses stratified by age, sex, study centre and adjusted for energy intake, smoking status, BMI, educational level, diabetes status, supplement use and dietary fibre intake, we found no significant association between folate intake and PC risk: the HR of PC risk for those in the highest quartile of folate intake (≥353 μg/d) compared with the lowest (<241 μg/d) was 0.81 (95% CI: 0.51, 1.31; Ptrend = 0.38). In current smokers, a positive trend was observed in PC risk across folate quartiles (HR=4.42 (95% CI: 1.05, 18.62) for ≥353 μg/d vs. <241 μg/d, Ptrend = 0.01). Nonetheless, there was no significant interaction between smoking and dietary folate intake (Pinteraction = 0.99). We found no association between dietary folate intake and PC risk in this large European study. This article is protected by copyright. All rights reserved.
    • Decision models of prediabetes populations: a systematic review.

      Leal, Jose; Morrow, Liam Mc; Kurshid, Waqar; Pagano, Eva; Feenstra, Talitha (2019-03-03)
      With evidence supporting the use of preventive interventions for prediabetes populations and the use of novel biomarkers to stratify the risk of progression there is a need to evaluate their cost-effectiveness across jurisdictions. Our aim is to summarise and assess the quality and validity of decision models and model-based economic evaluations of populations with prediabetes, evaluate their potential use for the assessment of novel prevention strategies and discuss the knowledge gaps, challenges and opportunities. We searched Medline, Embase, EconLit and NHS EED between 2000 and 2018 for studies reporting computer simulation models of the natural history of individuals with prediabetes and/or used decision models to evaluate the impact of treatment strategies on these populations. Data were extracted following PRISMA guidelines and assessed using modelling checklists. Two reviewers independently assessed 50% of the titles and abstracts to determine whether a full text review was needed. Of these, 10% was assessed by each reviewer to cross-reference the decision to proceed to full review. Using a standardised form, and double extraction, four reviewers each extracted 50% of identified studies. Twenty-nine published decision models that simulate prediabetes populations were identified. Studies showed large variations in the definition of prediabetes and model structure. The inclusion of complications in prediabetes (n=8) and type 2 diabetes (n=17) health states also varied. A minority of studies simulated annual changes in risk factors (glycaemia, HbA1c, blood pressure, BMI, lipids) as individuals progressed in the models (n=7) and accounted for heterogeneity amongst individuals with prediabetes (n=7). Current prediabetes decision models have considerable limitations in terms of their quality and validity and are not equipped to evaluate stratified strategies using novel biomarkers highlighting a clear need for more comprehensive prediabetes decision models. This article is protected by copyright. All rights reserved.
    • Diet, Physical Activity, and Daylight Exposure Patterns in Night-Shift Workers and Day Workers.

      van de Langenberg, Daniella; Vlaanderen, Jelle J; Dollé, Martijn E T; Rookus, Matti A; van Kerkhof, Linda W M; Vermeulen, Roel C H (2019-01-07)
      Night-shift work has been reported to have an impact on nutrition, daylight exposure, and physical activity, which might play a role in observed health effects. Because these exposures show diurnal variation, and shift work has been related with disturbances in the circadian rhythm, the timing of assessment of these factors requires careful consideration. Our aim was to describe the changes in patterns of diet, physical activity, and daylight exposure associated with night-shift work. We conducted an observational study among female healthcare workers either regularly working night shifts or not working night shifts. We assessed physical activity and daylight exposure using continuous monitoring devices for 48 h. We logged dietary patterns (24 h) and other health- and work-associated characteristics. Two measurement sessions were conducted when participants did 'not' work night shifts, and one session was conducted during a night-shift period. Our study included 69 night-shift workers and 21 day workers. On days in which they conduct work but no night work, night-shift workers had similar physical activity and 24-h caloric intake, yet higher overall daylight exposures than day workers and were more often exposed around noon instead of mainly around 1800h. Night-shift workers were less exposed to daylight during the night-shift session compared to the non-night-shift session. Total caloric intakes did not significantly differ between sessions, but we did observe a shorter maximum fasting interval, more eating moments, and a higher percentage of fat intake during the night-shift session. Observed differences in diet, physical activity, and exposure to daylight primarily manifested themselves through changes in exposure patterns, highlighting the importance of time-resolved measurements in night-shift-work research. Patterns in daylight exposure were primarily related to time of waking up and working schedule, whereas timing of dinner seemed primarily governed by social conventions.
    • The contribution of work and lifestyle factors to socioeconomic inequalities in self-rated health ‒ a systematic review.

      Dieker, Amy Cm; IJzelenberg, Wilhelmina; Proper, Karin I; Burdorf, Alex; Ket, Johannes Cf; van der Beek, Allard J; Hulsegge, Gerben (2019-03-01)
      Objective This study aimed to systematically review the literature on the contribution of work and lifestyle factors to socioeconomic inequalities in self-rated health among workers. Methods A search for cross-sectional and longitudinal studies assessing the contribution of work and/or lifestyle factors to socioeconomic inequalities in self-rated health among workers was performed in PubMed, PsycINFO and Web of Science in March 2017. Two independent reviewers performed eligibility and risk of bias assessment. The median change in odds ratio between models without and with adjustment for work or lifestyle factors across studies was calculated to quantify the contribution of work and lifestyle factors to health inequalities. A best-evidence synthesis was performed. Results Of those reviewed, 3 high-quality longitudinal and 17 cross-sectional studies consistently reported work factors to explain part (about one-third) of the socioeconomic health inequalities among workers (grade: strong evidence). Most studies separately investigated physical and psychosocial work factors. In contrast with the 12 cross-sectional studies, 2 longitudinal studies reported no separate contribution of physical workload and physical work environment to health inequalities. Regarding psychosocial work factors, lack of job resources (eg, less autonomy) seemed to contribute to health inequalities, whereas job demands (eg, job overload) might not. Furthermore, 2 longitudinal and 4 cross-sectional studies showed that lifestyle factors explain part (about one-fifth) of the health inequalities (grade: strong evidence). Conclusions The large contribution of work factors to socioeconomic health inequalities emphasizes the need for future longitudinal studies to assess which specific work factors contribute to health inequalities.
    • The Combined Effect of Cancer and Cardio-Metabolic Conditions on the Mortality Burden in Older Adults.

      Raina, Parminder; Gilsing, Anne; Freisling, Heinz; van den Heuvel, Edwin; Sohel, Nazmul; Jenab, Mazda; Ferrari, Pietro; Tjønneland, Anne; Benetou, Vassiliki; Picavet, Susan; et al. (2018-03-19)
      The number of older people living with cancer and cardio-metabolic conditions is increasing but little is known about how specific combinations of these conditions impact mortality.
    • Controlled human infection with Bordetella pertussis induces asymptomatic, immunising colonisation.

      de Graaf, H; Ibrahim, M; Hill, A R; Gbesemete, D; Vaughan, A T; Gorringe, A; Preston, A; Buisman, A M; Faust, S N; Kester, K E; et al. (2019-09-28)
    • The effect of salting on Toxoplasma gondii viability evaluated and implemented in a quantitative risk assessment of meat-borne human infection.

      Deng, Huifang; Swart, Arno; Bonačić Marinović, Axel A; van der Giessen, Joke W B; Opsteegh, Marieke (2019-10-30)
    • An ecological perspective on a river's rights: a recipe for more effective water quality.governance?

      Wuijts, S; Beekman, J; van der Wal, B; Suykens, C; Driessen, PPJ; van Rijswick, HFMW (2019-01-02)
    • The effects of increasing land use intensity on soil nematodes: A turn towards specialism

      Vazquez, C; Korthals GW; de Goede, RGM; Rutgers, M; Schouten, AJ; Creamer, R (2019-08-26)
    • Impact of NBS for VLCAD deficiency on genetic, enzymatic and clinical outcomes.

      Bleeker, Jeannette C; Kok, Irene L; Ferdinandusse, Sacha; van der Pol, W Ludo; Cuppen, Inge; Bosch, Annet M; Langeveld, Mirjam; Derks, Terry G J; Williams, Monique; de Vries, Maaike; et al. (2019-02-13)
      Most infants with very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) identified by newborn screening (NBS) are asymptomatic at the time of diagnosis and remain asymptomatic. If this outcome is due to prompt diagnosis and initiation of therapy, or because of identification of individuals with biochemical abnormalities who will never develop symptoms, is unclear. A 10 year longitudinal national cohort study of genetically confirmed VLCADD patients born before and after introduction of NBS. Main outcome measures were clinical outcome parameters, ACADVL gene analysis, VLCAD activity and overall capacity of long-chain fatty acid oxidation (LC-FAO flux) in lymphocytes and cultured skin fibroblasts. Median VLCAD activity in lymphocytes of 54 patients, 21 diagnosed pre-NBS and 33 by NBS was respectively 5.4% (95% CI 4.0-8.3%) and 12.6% (95% CI 10.7-17.7%; p<.001) of the reference mean. The median LC-FAO flux was 33.2% (95% CI 22.8-48.3%) and 41% (95% CI 40.8-68%; p<.05) of the control mean, respectively. Clinical characteristics in 23 pre-NBS and 37 NBS patients revealed hypoglycemic events in 12 versus 2 patients, cardiomyopathy in 5 versus 4 patients and myopathy in 14 versus 3 patients. All patients with LC-FAO flux <10% developed symptoms. Of the patients with LC-FAO flux >10% 7 out of 12 diagnosed pre-NBS versus none by NBS experienced hypoglycemic events. NBS has a clear beneficial effect on the prevention of hypoglycemic events in patients with some residual enzyme activity, but does not prevent hypoglycemia nor cardiac complications in patients with very low residual enzyme activity. The effect of NBS on prevalence and prevention of myopathy-related complications remains unclear.
    • Integrating Clinical and Epidemiologic Data on Allergic Diseases Across Birth Cohorts: A Harmonization Study in the Mechanisms of the Development of Allergy Project.

      Benet, Marta; Albang, Richard; Pinart, Mariona; Hohmann, Cynthia; Tischer, Christina G; Annesi-Maesano, Isabella; Baïz, Nour; Bindslev-Jensen, Carsten; Lødrup Carlsen, Karin C; Carlsen, Kai-Hakon; et al. (2019-02-01)
      The numbers of international collaborations among birth cohort studies designed to better understand asthma and allergies have increased in the last several years. However, differences in definitions and methods preclude direct pooling of original data on individual participants. As part of the Mechanisms of the Development of Allergy (MeDALL) Project, we harmonized data from 14 birth cohort studies (each with 3-20 follow-up periods) carried out in 9 European countries during 1990-1998 or 2003-2009. The harmonization process followed 6 steps: 1) organization of the harmonization panel; 2) identification of variables relevant to MeDALL objectives (candidate variables); 3) proposal of a definition for each candidate variable (reference definition); 4) assessment of the compatibility of each cohort variable with its reference definition (inferential equivalence) and classification of this inferential equivalence as complete, partial, or impossible; 5) convocation of a workshop to agree on the reference definitions and classifications of inferential equivalence; and 6) preparation and delivery of data through a knowledge management portal. We agreed on 137 reference definitions. The inferential equivalence of 3,551 cohort variables to their corresponding reference definitions was classified as complete, partial, and impossible for 70%, 15%, and 15% of the variables, respectively. A harmonized database was delivered to MeDALL investigators. In asthma and allergy birth cohorts, the harmonization of data for pooled analyses is feasible, and high inferential comparability may be achieved. The MeDALL harmonization approach can be used in other collaborative projects.
    • Pure fruit juice and fruit consumption and the risk of CVD: the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) study.

      Scheffers, Floor R; Boer, Jolanda M A; Verschuren, W M Monique; Verheus, Martijn; van der Schouw, Yvonne T; Sluijs, Ivonne; Smit, Henriëtte A; Wijga, Alet H (2019-02-01)
      Dietary guidelines for pure fruit juice consumption differ between countries, regarding the question whether pure fruit juice is an acceptable alternative for fruit. Currently, little is known about pure fruit juice consumption and the risk of CVD. In this prospective cohort study, we studied the association of pure fruit juice and fruit consumption with the incidence of fatal and non-fatal CVD, CHD and stroke and investigated the differences in association with pure fruit juice consumption between low and high fruit consumers. A validated FFQ was used to estimate dietary intake of 34 560 participants (26·0 % men and 74·0 % women) aged 20-69 years from the European Prospective Investigation into Cancer and Nutrition-Netherlands study. Adjusted hazard ratios (HR) were estimated using Cox regression after average follow-up of 14·6 years. Compared with no consumption, pure fruit juice consumption up to 7 glasses/week - but not consumption of ≥8 glasses - was significantly associated with reduced risk of CVD and CHD, with HR from 0·83 (95 % CI 0·73, 0·95) to 0·88 (95 % CI 0·80, 0·97). Consumption of 1-4 and 4-8 glasses/week was significantly associated with lower risk of stroke with HR of 0·80 (95 % CI 0·64, 0·99) and 0·76 (95 % CI 0·61, 0·94), respectively. Associations did not differ considerably between low and high fruit consumers. The highest three quintiles of fruit consumption (≥121 g/d) were significantly associated with lower incidence of CVD, with HR of 0·87 (95 % CI 0·78, 0·97) and 0·88 (95 % CI 0·80, 0·98). In conclusion, although we observed favourable associations of moderate pure fruit juice consumption with CVD, for now consumption of whole fruit should be preferred because the evidence of the health benefits of fruit is more conclusive.
    • Road-killed mammals provide insight into tick-borne bacterial pathogen communities within urban habitats.

      Szekeres, Sándor; Docters van Leeuwen, Arieke; Tóth, Evelin; Majoros, Gábor; Sprong, Hein; Földvári, Gábor (2018-09-19)
      Small- and medium-sized mammals play an important role in the life cycle of tick-borne pathogens in urban habitats. Our aim was to apply the general protocol, DAMA (documentation-assessment-monitoring-action), which is an integrated proposal to build a proactive capacity to understand, anticipate, and respond to the outcomes of accelerating environmental change. Here we tested whether road-killed carcasses in urban areas are useful sources of tissue and parasite samples to investigate these species' contribution to the epidemiology of vector-borne diseases. We collected 29 road-killed and 6 carcasses with different causes of mortality (23 northern white-breasted hedgehogs and 12 from seven other mammal species) mainly from Budapest, Hungary. We used quantitative and conventional PCRs to determine pathogens in 90 collected tissues (52 from hedgehogs; 38 from other species) and 417 ticks that were only found on hedgehogs. Tissue samples revealed a wide range of bacteria including human zoonotic pathogens identified as Anaplasma phagocytophilum ecotype I, Borrelia afzelii, B. spielmanii, Borrelia miyamotoi, Rickettsia helvetica, and Bartonella species. Among the 23 collected hedgehog carcasses, 17 (74%) were infected with A. phagocytophilum, 6 (26%) with Borrelia burgdorferi s.l., 12 (52%) with R. helvetica, and 15 (65%) with Rickettsia sp. Furthermore, we report the first detection of Rickettsia sp. infection in European moles and lesser weasel and R. helvetica in stone marten. Through sequencing B. afzelii, R. helvetica, R. monacensis and A. phagocytophilum ecotype I were identified in the ticks removed from the carcasses. We showed that road-killed urban mammal species are exposed to multiple tick-borne pathogens but further studies have to clarify whether they, in fact, also have a role in their maintenance and spread. Our study also demonstrates that roadkill can be used in the risk assessment of potential human infection and in the implementation of the DAMA protocol.
    • QSAR-based estimation of SSD parameters - an exploratory investigation.

      Hoondert, Renske; Oldenkamp, Rik; de Zwart, Dick; van de Meent, Dik; Posthuma, Leo (2019-09-25)
      Ecological risk assessments are hampered by limited availability of ecotoxicity data. The present study aimed to explore the possibility of deriving SSD (species sensitivity distribution) parameters for non-tested compounds, based on simple physicochemical characteristics, known SSDs for data-rich compounds and a QSAR-type approach. The median toxicity of a data-poor chemical for species assemblages significantly varies with values of the physicochemical descriptors, especially when based on high quality SSD data (either from acute EC50 s or chronic NOECs). Beyond exploratory uses, we discussed how the precision of QSAR-based SSDs can be improved to construct models that accurately predict the SSD-parameters of data poor chemicals. The current models show that the concept of QSAR-based SSDs supports screening-level evaluations of the potential ecotoxicity of compounds for which data are lacking. This article is protected by copyright. All rights reserved.
    • Paternal cholestasis exacerbates obesity-associated hypertension in male offspring but is prevented by paternal ursodeoxycholic acid treatment.

      Pataia, Vanessa; Papacleovoulou, Georgia; Nikolova, Vanya; Samuelsson, Anne-Maj; Chambers, Stephanie; Jansen, Eugene; Taylor, Paul D; Poston, Lucilla; Williamson, Catherine (2018-05-24)
      Obesity is a heterogeneous phenotype and risk associations to non-communicable diseases such as cardiovascular disease and type 2 diabetes are influenced by several factors. The paternal metabolic status at the time of conception influences offspring susceptibility to developing obesity and adiposity-associated cardiometabolic disease. Cholestatic liver diseases are characterized by raised circulating serum bile acid levels and dyslipidemia, and are commonly treated with ursodeoxycholic acid (UDCA). We hypothesized that paternal cholestasis alters offspring susceptibility to developing obesity and adiposity-associated cardiometabolic disease and that this may be modified by paternal UDCA treatment.
    • A nationwide retrospective observational study of population newborn screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in the Netherlands.

      Jager, Emmalie A; Kuijpers, Myrthe M; Bosch, Annet M; Mulder, Margot F; Gozalbo, Estela R; Visser, Gepke; de Vries, Maaike; Williams, Monique; Waterham, Hans R; van Spronsen, Francjan J; et al. (2019-09-01)
    • Pain over the adult life course: 15-year pain trajectories-The Doetinchem Cohort Study.

      Picavet, H Susan J; Monique Verschuren, W M; Groot, Lichelle; Schaap, Laura; van Oostrom, Sandra H (2019-10-01)
    • Coffee and tea consumption and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition.

      Sen, Abhijit; Papadimitriou, Nikos; Lagiou, Pagona; Perez-Cornago, Aurora; Travis, Ruth C; Key, Timothy J; Murphy, Neil; Gunter, Marc; Freisling, Heinz; Tzoulaki, Ioanna; et al. (2018-06-26)
      The epidemiological evidence regarding the association of coffee and tea consumption with prostate cancer risk is inconclusive, and few cohort studies have assessed these associations by disease stage and grade. We examined the associations of coffee (total, caffeinated and decaffeinated) and tea intake with prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 142,196 men, 7,036 incident prostate cancer cases were diagnosed over 14 years of follow-up. Data on coffee and tea consumption were collected through validated country-specific food questionnaires at baseline. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CI). Models were stratified by center and age, and adjusted for anthropometric, lifestyle and dietary factors. Median coffee and tea intake were 375 mL/day and 106 mL/day, respectively, but large variations existed by country. Comparing the highest (median of 855 mL/day) versus lowest (median of 103 mL/day) consumers of coffee and tea (450 mL/day versus 12 mL/day) the HRs were 1.02 (95% CI, 0.94-1.09) and 0.98 (95% CI, 0.90-1.07) for risk of total prostate cancer, and 0.97 (95% CI, 0.79-1.21) and 0.89 (95% CI, 0.70-1.13) for risk of fatal disease, respectively. No evidence of association was seen for consumption of total, caffeinated or decaffeinated coffee or tea and risk of total prostate cancer or cancer by stage, grade or fatality in this large cohort. Further investigations are needed to clarify whether an association exists by different preparations or by concentrations and constituents of these beverages. This article is protected by copyright. All rights reserved.
    • CA19-9 and Apolipoprotein-A2 isoforms as detection markers for pancreatic cancer - a prospective evaluation.

      Honda, K; Katzke, V A; Hüsing, A; Okaya, S; Shoji, H; Onidani, K; Olsen, A; Tjønneland, A; Overvad, K; Weiderpass, E; et al. (2018-09-27)
      Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. This study provides a first prospective evaluation of an ApoA2 isoform ("ApoA2-ATQ/AT"), alone and in combination with carbohydrate antigen 19-9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6-18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6-18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6-18 or ≤18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging. This article is protected by copyright. All rights reserved.