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Background: In the Netherlands, population-based cancer screening programmes (CSPs) are organized aiming at cervical, breast and colorectal cancer. For a CSP to be effective, high participation rates are essential; however, there is an alarming downward trend, including wide regional variation in screening uptake. General practitioner (GP) involvement can have a stimulating effect on screening participation. Current GP involvement is however, limited, varies between the programmes and has changed over time. Unexplored is what GPs think of their role(s) in the CSPs. The aim of this study was therefore to map the perceptions and beliefs of GPs regarding their current and future role in the Dutch CSPs., Methods: A mixed-methods sequential explanatory study was conducted in the Leiden/The Hague area of the Netherlands, between the end of 2021 and 2022. A questionnaire was developed and distributed among 110 GPs. The aggregated results obtained from the questionnaires served as starting points for conducting semi-structured interviews, with purposefully selected GPs. With this sequential approach we aimed to further enhance the understanding of the questionnaire data, and delved into the topics that emerged from the questionnaire responses., Results: In total, 46 GPs completed the online questionnaire (response rate 42%). Subsequent five semi-structured comprehensive interviews were conducted. GPs indicated that they frequently encounter the CSP in their daily practice and consider it important. They also emphasised it is important that GPs remain closely involved with the CSPs in the future. Nevertheless, GPs also repeatedly mentioned that they are not eager to take on more logistical/organizational tasks. They are however willing to empower CSPs in a positive manner., Conclusion: GPs were generally positive about the CSPs and their current role within these programmes. Nevertheless, several options have been proposed to improve the CSPs, especially to increase screening uptake for populations in a socioeconomically disadvantaged position. Since it is of utmost importance to screen those who are most at risk of developing the screening-specific tumours, efforts should be made to achieve this goal., (© 2024. The Author(s).)

Objectives: Throughout Europe, many countries offer population-based cancer screening programmes (CSPs). In the Netherlands, two implemented CSPs are targeting people of 50 years and older, aiming at breast cancer (BC) and colorectal cancer (CRC). In order for a CSP to be (cost-)effective, high participation rates and outreach to the populations at risk are essential. People living in highly urbanised areas and big cities are known to participate less in CSPs. The aim of this study was to gain further insight into the participation patterns of a screening-eligible population of 50 years and over, living in a highly urbanised region, over a longer time period., Design: A retrospective observational study., Setting: Participation data of the regional screening organisation, linked to the cancer incidence data derived from the Netherlands Cancer Registry, concerning the city of The Hague, between 2005 and 2019. Attendance groups were defined as attenders (attending >50% of the invitations) and non-attenders (attending ≤50% of the invitations), and were mutually compared., Results: The databases contained 106 377 unique individuals on the BC screening programme (SP) and 73 669 on the CRC-SP. Non-attendance at both CSPs was associated with living in a lower socioeconomic status (SES) neighbourhood and as a counter effect, also associated with a more unfavourable, relatively late-stage, tumour diagnosis. When combining the results of the two CSPs, our results imply high screening adherence over time. Women who did not participate in both CSPs were older, and more often lived in neighbourhoods with a lower SES score., Conclusions: Since low screening uptake is one of the factors that contribute to increasing inequalities in cancer survival, future outreach strategies should be focused on engaging specific non-attending subgroups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study aimed to identify determinants of inappropriate antibiotic prescription in primary care in developed countries and to construct a framework with the determinants to help understand which actions can best be targeted to counteract development of antimicrobial resistance (AMR)., Design: A systematic review of peer-reviewed studies reporting determinants of inappropriate antibiotic prescription published through 9 September 2021 in PubMed, Embase, Web of Science and the Cochrane Library was performed., Setting: All studies focusing on primary care in developed countries where general practitioners (GPs) act as gatekeepers for referral to medical specialists and hospital care were included., Results: Seventeen studies fulfilled the inclusion criteria and were used for the analysis which identified 45 determinants of inappropriate antibiotic prescription. Important determinants for inappropriate antibiotic prescription were comorbidity, primary care not considered to be responsible for development of AMR and GP perception of patient desire for antibiotics. A framework was constructed with the determinants and provides a broad overview of several domains. The framework can be used to identify several reasons for inappropriate antibiotic prescription in a specific primary care setting and from there, choose the most suitable intervention(s) and assist in implementing them for combatting AMR., Conclusions: The type of infection, comorbidity and the GPs perception of a patient's desire for antibiotics are consistently identified as factors driving inappropriate antibiotic prescription in primary care. A framework with determinants of inappropriate antibiotic prescription may be useful after validation for effective implementation of interventions for decreasing these inappropriate prescriptions., Prospero Registration Number: CRD42023396225., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The present study aimed to early identify patients with persistent somatic symptoms (PSS) in primary care by exploring routine care data-based approaches., Design/setting: A cohort study based on routine primary care data from 76 general practices in the Netherlands was executed for predictive modelling., Participants: Inclusion of 94 440 adult patients was based on: at least 7-year general practice enrolment, having more than one symptom/disease registration and >10 consultations., Methods: Cases were selected based on the first PSS registration in 2017-2018. Candidate predictors were selected 2-5 years prior to PSS and categorised into data-driven approaches: symptoms/diseases, medications, referrals, sequential patterns and changing lab results; and theory-driven approaches: constructed factors based on literature and terminology in free text. Of these, 12 candidate predictor categories were formed and used to develop prediction models by cross-validated least absolute shrinkage and selection operator regression on 80% of the dataset. Derived models were internally validated on the remaining 20% of the dataset., Results: All models had comparable predictive values (area under the receiver operating characteristic curves=0.70 to 0.72). Predictors are related to genital complaints, specific symptoms (eg, digestive, fatigue and mood), healthcare utilisation, and number of complaints. Most fruitful predictor categories are literature-based and medications. Predictors often had overlapping constructs, such as digestive symptoms (symptom/disease codes) and drugs for anti-constipation (medication codes), indicating that registration is inconsistent between general practitioners (GPs)., Conclusions: The findings indicate low to moderate diagnostic accuracy for early identification of PSS based on routine primary care data. Nonetheless, simple clinical decision rules based on structured symptom/disease or medication codes could possibly be an efficient way to support GPs in identifying patients at risk of PSS. A full data-based prediction currently appears to be hampered by inconsistent and missing registrations. Future research on predictive modelling of PSS using routine care data should focus on data enrichment or free-text mining to overcome inconsistent registrations and improve predictive accuracy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Antibiotics are frequently prescribed during viral respiratory infection episodes in primary care. There is limited information about antibiotic prescription during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in primary care and its association with risk factors for an adverse course., Aim: To compare the proportion of antibiotic prescriptions between patients with COVID-19 and influenza or influenza-like symptoms, and to assess the association between antibiotic prescriptions and risk factors for an adverse course of COVID-19., Design & Setting: An observational cohort study using pseudonymised and coded routine healthcare data extracted from 85 primary care practices in the Netherlands., Method: Adult patients with influenza and influenza-like symptoms were included from the 2017 influenza season to the 2020 season. Adult patients with suspected or confirmed COVID-19 were included from the first (15 February 2020-1 August 2020) and second (1 August 2020-1 January 2021) SARS-CoV-2 waves. Proportions of antibiotic prescriptions were calculated for influenza and COVID-19 patients. Odds ratios (ORs) were used to compare the associations of antibiotic prescriptions in COVID-19 patients with risk factors, hospital admission, intensive care unit (ICU) admission, and mortality., Results: The proportion of antibiotic prescriptions during the first SARS-CoV-2 wave was lower than during the 2020 influenza season (9.6% versus 20.7%), difference 11.1% (95% confidence interval [CI] = 8.7 to 13.5). During the second SARS-CoV-2 wave, antibiotic prescriptions were associated with being aged ≥70 years (OR 2.05; 95% CI = 1.43 to 2.93), the number of comorbidities (OR 1.46; 95% CI = 1.18 to 1.82), and admission to hospital (OR 3.19; 95% CI = 2.02 to 5.03) or ICU (OR 4.64; 95% CI = 2.02 to 10.62)., Conclusion: Antibiotic prescription was less common during the SARS-CoV-2 pandemic than during influenza seasons, and was associated with an adverse course and its risk factors. The findings suggest a relatively targeted prescription policy of antibiotics in primary care during COVID-19., (Copyright © 2022, The Authors.)

Background: Proton pump inhibitor (PPI) indications are limited to gastrointestinal disorders and ulcer prophylaxis. However, PPIs are among the most frequently prescribed drugs., Aim: To evaluate the appropriateness of PPI prescriptions and identify predictive factors for inappropriate PPI use., Design and Setting: Observational study using a Dutch primary care database with all new PPI prescriptions between 2016 and 2018., Method: Individual patient data and details on PPI use were collected. The appropriateness of initiation and continuation of PPI prescriptions was evaluated using the applicable guidelines., Results: In total, 148 926 patients (aged ≥18 years) from 27 general practices were evaluated. A total of 23 601 (16%) patients started PPI therapy (mean age 57 [SD 17] years, 59% female). Valid PPI indications at initiation were seen in 10 466 PPI users (44%). Predictors for inappropriately initiated PPI use were older age (odds ratio [OR] 1.03, 95% confidence interval [CI] = 1.03 to 1.03), and use of non-selective non-steroidal anti-inflammatory drugs (OR 5.15, 95% CI = 4.70 to 5.65), adenosine diphosphate receptor inhibitors (OR 5.07, 95% CI = 3.46 to 7.41), COX-2 inhibitors (also known as coxibs) (OR 3.93, 95% CI = 2.92 to 5.28), and low-dose aspirin (OR 3.83, 95% CI = 3.07 to 4.77). Despite an initial valid indication, PPI use was inaccurately continued in 32% of patients on short-course therapy for dyspepsia and in 11% of patients on ulcer prophylaxis., Conclusion: More than half of PPI users in primary care were found to have an inappropriate indication, with unnecessary ulcer prophylaxis related to drug use being one of the leading causes. Future initiatives to reduce PPI use for unnecessary ulcer prophylaxis and timely deprescription if PPI is no longer indicated, are needed., (© The Authors.)

Background: The Netherlands hosts, as many other European countries, three population-based cancer screening programmes (CSPs). The overall uptake among these CSPs is high, but has decreased over recent years. Especially in highly urbanized regions the uptake rates tend to fall below the minimal effective rate of 70% set by the World Health Organization. Understanding the reasons underlying the decision of citizens to partake in a CPS are essential in order to optimize the current screening participation rates. The aim of this study was to explore the various perspectives concerning cancer screening among inhabitants of The Hague, a highly urbanized region of the Netherlands., Methods: A Q-methodology study was conducted to provide insight in the prevailing perspectives on partaking in CSPs. All respondents were inhabitants of the city of The Hague, the Netherlands. In an online application they ranked a set of 31 statements, based on the current available literature and clustered by the Integrated Change model, into a 9-column forced ranking grid according to level of agreement, followed by a short survey. Respondents were asked to participate in a subsequent interview to explain their ranking. By-person factor analysis was used to identify distinct perspectives, which were interpreted using data from the rankings and interviews., Results: Three distinct perspectives were identified: 1). "Positive about participation", 2). "Thoughtful about participation", and 3). "Fear drives participation". These perspectives provide insight into how potential respondents, living in an urbanized region in the Netherlands, decide upon partaking in CSPs., Conclusions: Since CSPs will only be effective when participation rates are sufficiently high, it is essential to have insight into the different perspectives among potential respondents concerning partaking in a CSP. This study adds new insights concerning these perspectives and suggests several ideas for future optimization of the CSPs., (© 2022. The Author(s).)

Background: Approximately 2% of patients in primary care practice and up to 25% of hospital patients are registered as being allergic to an antibiotic. However, up to 90% of these registrations are incorrect, leading to unnecessary prescription of 2nd choice antibiotics with the attendant loss of efficacy, increased toxicity and antibiotic resistance. To improve registration, a better understanding is needed of how incorrect labels are attributed., Objective: To investigate the quality of antibiotic allergy registration in primary care and identify determinants to improve registration of antibiotic allergies., Design: Registration of antibiotic allergies in primary care practices were analysed for 1) completeness and 2) correctness. To identify determinants for improvement, semi-structured interviews with healthcare providers from four healthcare domains were conducted., Participants: A total of 300 antibiotic allergy registrations were analysed for completeness and correctness. Thirty-four healthcare providers were interviewed., Main Measures: A registration was defined as complete when it included a description of all symptoms, time to onset of symptoms and the duration of symptoms. It was defined as correct when the conclusion was concordant with the Salden criteria. Determinants of correct antibiotic allergy registrations were divided into facilitators or obstructers., Key Results: Rates of completeness and correctness of registrations were 0% and 29.3%, respectively. The main perceived barriers for correct antibiotic allergy registration were insufficient knowledge, lack of priority, limitations of registration features in electronic medical records (EMR), fear of medical liability and patients interpreting side-effects as allergies., Conclusions: The quality of antibiotic allergy registrations can be improved. Potential interventions include raising awareness of the consequences of incomplete and the importance of correct registrations, by continued education, and above all simplifying registration in an EMR by adequate ICT support., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To investigate the potential value of combining information from electronic health records from Dutch general practitioners (GPs) and preventive youth healthcare professionals (PYHPs) in predicting child mental health problems (MHPs)., Design: Population-based retrospective cohort study., Setting: General practice, children who were registered with 76 general practice centres from the Leiden University Medical Centre (LUMC) primary care academic network Extramural LUMC Academic Network in the Leiden area, the Netherlands. For the included children we obtained data regarding a child's healthy development from preventive youth healthcare., Participants: 48 256 children aged 0-19 years old who were registered with participating GPs between 2007 and 2017 and who also had data available from PYHPs from the period 2010-2015. Children with MHPs before 2007 were excluded (n=3415)., Primary Outcome: First MHPs based on GP data., Results: In 51% of the children who had MHPs according to GPs, PYPHs also had concerns for MHPs. In 31% of the children who had no MHPs according to GPs, PYHPs had recorded concerns for MHPs. Combining their information did not result in better performing prediction models than the models based on GP data alone (c-statistics ranging from 0.62 to 0.64). Important determinants of identification of MHPs by PYHPs 1 year later were concerns from PHYPs about MHPs, borderline or increased problem scores on mental health screening tools, life events, family history of MHPs and an extra visit to preventive youth healthcare., Conclusions: Although the use of combined information from PYHPs and GPs did not improve prediction of MHPs compared with the use of GP data alone, this study showed the feasibility of analysing a combined dataset from different healthcare providers what has the potential to inform future studies aimed at improving child MHP identification., Competing Interests: Competing interests: All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years, no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Many countries organize population-based cervical cancer screening programs (CSP). In the Netherlands, eligible women are invited by mail. Marginalized women living in unstable conditions and homeless women often fail to receive the invitation letter. These women also experience access barriers to regular healthcare. Consequently, despite presumably being at higher risk of developing cervical cancer due to prevalent risk factors, marginalized women are rarely screened for cervical cancer. The aim of the study was to identify the prevalence of (pre)cancerous abnormalities among marginalized women, and subsequently explore invitation approaches to enhance their screening participation., Methods: A cross-sectional intervention study was conducted in Rotterdam, the Netherlands. Between February and May 2019, marginalized women aged 20-60 years were invited to participate in cervical screening. A participant was considered screen-positive when they tested positive for high-risk human papilloma virus (HR-HPV) and showed cytological abnormalities. Data of the study population were compared with regional data of the Dutch CSP. Various invitation approaches were used to recruit women., Results: Out of 74 included women, 12 participants (16%) were found screen-positive, against 3.4% in women screened by the Dutch CSP. The prevalence ratio for the study population was 4.4 (95% CI 1.9-8.6) compared with women screened by the Dutch CSP. Using a direct, pro-active approach resulted in participation of 92% of the included women., Conclusion: Marginalized women have an increased risk of (pre)cancerous cervical abnormalities in screening, compared with women screened by the Dutch CSP. A direct pro-active approach was the most effective to stimulate screening participation. Enhancement of screening uptake for this population needs special effort., Competing Interests: The authors report no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors received non-financial support from the Netherlands Streetdoctors Group, non-financial support from Erasmus Medical Center, and non-financial support from Stichting Bevolkingsonderzoek Zuid-West., (© 2021 Bongaerts et al.)

Background and Objectives: Early identification of child mental health problems (MHPs) is important to provide adequate, timely treatment. Dutch preventive youth healthcare monitors all aspects of a child's healthy development. We explored the usefulness of their electronic health records (EHRs) in scientific research and aimed to develop prediction models for child MHPs. Methods: Population-based cohort study with anonymously extracted electronic healthcare data from preventive youth healthcare centers in the Leiden area, the Netherlands, from the period 2005-2015. Data was analyzed with respect to its continuity, percentage of cases and completeness. Logistic regression analyses were conducted to develop prediction models for the risk of a first recorded concern for MHPs in the next scheduled visit at age 3/4, 5/6, 10/11, and 13/14 years. Results: We included 26,492 children. The continuity of the data was low and the number of concerns for MHPs varied greatly. A large number of determinants had missing data for over 80% of the children. The discriminatory performance of the prediction models were poor. Conclusions: This is the first study exploring the usefulness of EHRs from Dutch preventive youth healthcare in research, especially in predicting child MHPs. We found the usefulness of the data to be limited and the performance of the developed prediction models was poor. When data quality can be improved, e.g., by facilitating accurate recording, or by data enrichment from other available sources, the analysis of EHRs might be helpful for better identification of child MHPs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Koning, Büchner, van den Berg, Choi, Leeuwenburgh, Paijmans, van Dijk-van Dijk, Numans and Crone.)

Background: Disease clustering is a growing public health concern and is increasingly linked to adverse socioeconomic conditions. Few population-based studies have focussed on interaction between non-communicable diseases. In this cross-sectional study, we examine clustering of, and synergistic interactions between, frequently occurring non-communicable diseases in Katwijk, a former fishing village in the Netherlands. Additionally, our study identifies contextual variables associated with these clusters of non-communicable diseases., Methods: In a survey among adults (>19 years) living in the former fishing village Katwijk, Netherlands, were asked about non-communicable diseases, psychological distress, self-rated health scores and contextual factors, eg, socio-demographic, psychosocial and health behavior characteristics. Interaction was measured on the additive and the multiplicative scale. We used generalized ordered logistic regression analysis to examine associations with contextual variables., Results: Three disease clusters were found to be most prevalent among the study participants (n = 1408). Each cluster involved a combination of frequently occurring conditions in this population: psychological distress (n = 261, 19%), cardiometabolic diseases (n = 449, 32%) and musculoskeletal pain (n = 462, 33%). These three diseases interact synergistically on the additive scale to increase the odds of reporting a low self-rated health. None of the disease clusters showed a statistically significant positive interaction on a multiplicative scale. Multiple contextual factors were associated with these disease clusters, including gender, loneliness, experiencing financial stress, and a BMI≥30., Conclusion: Our findings imply that psychological distress, cardiometabolic diseases and musculoskeletal pain synergistically interact, leading to a much lower self-rated health than expected. Several contextual factors are related to this interaction emphasizing the importance of a multicomponent, ecological approach., Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no conflicts of interest., (Copyright © 2021 by the Journal of Global Health. All rights reserved.)

Background: eHealth promises to increase self-management and personalised medicine and improve cost-effectiveness in primary care. Paired with these promises are ethical implications, as eHealth will affect patients' and primary care professionals' (PCPs) experiences, values, norms, and relationships. Objectives: We argue what ethical implications related to the impact of eHealth on four vital aspects of primary care could (and should) be anticipated. Discussion: (1) EHealth influences dealing with predictive and diagnostic uncertainty. Machine-learning based clinical decision support systems offer (seemingly) objective, quantified, and personalised outcomes. However, they also introduce new loci of uncertainty and subjectivity. The decision-making process becomes opaque, and algorithms can be invalid, biased, or even discriminatory. This has implications for professional responsibilities and judgments, justice, autonomy, and trust. (2) EHealth affects the roles and responsibilities of patients because it can stimulate self-management and autonomy. However, autonomy can also be compromised, e.g. in cases of persuasive technologies and eHealth can increase existing health disparities. (3) The delegation of tasks to a network of technologies and stakeholders requires attention for responsibility gaps and new responsibilities. (4) The triangulate relationship: patient-eHealth-PCP requires a reconsideration of the role of human interaction and 'humanness' in primary care as well as of shaping Shared Decision Making. Conclusion: Our analysis is an essential first step towards setting up a dedicated ethics research agenda that should be examined in parallel to the development and implementation of eHealth. The ultimate goal is to inspire the development of practice-specific ethical recommendations.

Objective: The Netherlands host three population-based cancer screening programmes: for cervical, breast, and colorectal cancer. For screening programmes to be effective, high participation rates are essential, but participation in the Netherlands' programmes is starting to fall below the minimal effective rate. We aimed to produce a systematic overview of the current known determinants of (non-)attendance at the Dutch cancer screening programmes., Methods: A literature search was conducted in the electronic databases Academic Search Premier, Cochrane Library, Embase, EMCare, PubMed, PsycINFO, Web of Science, and also in grey literature, including all articles published before February 2018. The I-Change model was used to categorize the identified determinants of cancer screening attendance., Results: In total, 19/1232 identified studies and 6 grey literature reports were included. Fifteen studies reported on predisposing factors. Characteristics such as social economic status, country of birth, and residency were most often reported, and correlate with cancer screening attendance. Thirteen studies addressed information factors. Factors on awareness, motivation, ability, and barriers were less often studied., Conclusion: Current studies tend to describe the general characteristics of (non-)attendance and (non-)attenders, but rarely provide in depth information on other factors of (non-)participation. The I-Change model proved to be a useful tool in mapping current knowledge on cancer screening attendance and revealed knowledge gaps regarding determinants of (non-)participation in the screening programmes. More research is needed to fully understand determinants of participation, in order to influence and optimize attendance rates over the long term.

Background: Despite being common and having long lasting effects, mental health problems in children are often under-recognised and under-treated. Improving early identification is important in order to provide adequate, timely treatment. We aimed to develop prediction models for the one-year risk of a first recorded mental health problem in children attending primary care., Methods: We carried out a population-based cohort study based on readily available routine healthcare data anonymously extracted from electronic medical records of 76 general practice centers in the Leiden area, the Netherlands. We included all patients aged 1-19 years on 31 December 2016 without prior mental health problems. Multilevel logistic regression analyses were used to predict the one-year risk of a first recorded mental health problem. Potential predictors were characteristics related to the child, family and healthcare use. Model performance was assessed by examining measures of discrimination and calibration., Findings: Data from 70,000 children were available. A mental health problem was recorded in 27•7% of patients during the period 2007-2017. Age independent predictors were somatic complaints, more than two GP visits in the previous year, one or more laboratory test and one or more referral/contact with other healthcare professional in the previous year. Other predictors and their effects differed between age groups. Model performance was moderate ( c -statistic 0.62-0.63), while model calibration was good., Interpretation: This study is a first promising step towards developing prediction models for identifying children at risk of a first mental health problem to support primary care practice by using routine healthcare data. Data enrichment from other available sources regarding e.g. school performance and family history could improve model performance. Further research is needed to externally validate our models and to establish whether we are able to improve under-recognition of mental health problems., Competing Interests: The authors declared to have no declaration of interest., (© 2019 Published by Elsevier Ltd.)

Background: Although common and often with long-lasting effects, child mental health problems (MHPs) are still under-recognized and under-treated. A better understanding of the factors associated with the identification of MHPs in primary care may improve the recognition of MHPs. Objectives: To review studies on factors associated with the identification of child MHPs in primary care. Methods: Six leading databases were systematically searched until 1 October 2018. Two independent researchers selected articles and extracted data on study characteristics and factors associated with MHP identification. Inclusion criteria were the investigation of factors associated with MHP identification by primary care professionals (PCPs) in children aged 0-18 years. Results: Of the 6215 articles identified, 26 were included. Prevalence rates of PCP-identified MHPs varied between 7 and 30%. PCPs identified 26-60% of children with an increased risk of MHPs as indicated by MHP assessment tools, but associated factors were investigated in relatively few studies. MHPs were more often identified in children with a family composition other than married parents, with worse mental health symptoms, prior MHPs, among boys in elementary school, when contact with PCPs was related to parental psychosocial concerns or routine health check-ups, when PCPs were recently trained in MHPs or when PCPs felt less burdened treating MHPs. Conclusion: MHP identification varied substantially between studies and PCPs and was related to several child, family and practice factors. Future studies should systematically investigate factors associated with MHP identification by PCPs and specifically in children with an increased risk of MHPs according to mental health assessment tools.

Background: Published associations between dietary carotenoids and vitamin C and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status., Objective: We investigated the association between plasma carotenoids and vitamin C and risk of urothelial cell carcinoma (UCC) in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition., Design: A total of 856 patients with newly diagnosed UCC were matched with 856 cohort members by sex, age at baseline, study center, date and time of blood collection, and fasting status. Plasma carotenoids (α- and β-carotene, β-cryptoxanthin, lycopene, lutein, and zeaxanthin) were measured by using reverse-phase HPLC, and plasma vitamin C was measured by using a colorimetric assay. Incidence rate ratios (IRRs) were estimated by using conditional logistic regression with adjustment for smoking status, duration, and intensity., Results: UCC risk decreased with higher concentrations of the sum of plasma carotenoids (IRR for the highest compared with the lowest quartile: 0.64; 95% CI: 0.44, 0.93; P-trend = 0.04). Plasma β-carotene was inversely associated with aggressive UCC (IRR: 0.51; 95% CI: 0.30, 0.88; P-trend = 0.02). Plasma lutein was inversely associated with risk of nonaggressive UCC (IRR: 0.56; 95% CI: 0.32, 0.98; P-trend = 0.05). No association was observed between plasma vitamin C and risk of UCC., Conclusions: Although residual confounding by smoking or other factors cannot be excluded, higher concentrations of plasma carotenoids may reduce risk of UCC, in particular aggressive UCC. Plasma lutein may reduce risk of nonaggressive UCC.

Fruit and vegetable intake (FVI) may reduce the risk of type 2 diabetes (T2D), but the epidemiological evidence is inconclusive. The aim of this study is to examine the prospective association of FVI with T2D and conduct an updated meta-analysis. In the European Prospective Investigation into Cancer-InterAct (EPIC-InterAct) prospective case-cohort study nested within eight European countries, a representative sample of 16,154 participants and 12,403 incident cases of T2D were identified from 340,234 individuals with 3.99 million person-years of follow-up. For the meta-analysis we identified prospective studies on FVI and T2D risk by systematic searches of MEDLINE and EMBASE until April 2011. In EPIC-InterAct, estimated FVI by dietary questionnaires varied more than twofold between countries. In adjusted analyses the hazard ratio (95% confidence interval) comparing the highest with lowest quartile of reported intake was 0.90 (0.80-1.01) for FVI; 0.89 (0.76-1.04) for fruit and 0.94 (0.84-1.05) for vegetables. Among FV subtypes, only root vegetables were inversely associated with diabetes 0.87 (0.77-0.99). In meta-analysis using pooled data from five studies including EPIC-InterAct, comparing the highest with lowest category for FVI was associated with a lower relative risk of diabetes (0.93 (0.87-1.00)). Fruit or vegetables separately were not associated with diabetes. Among FV subtypes, only green leafy vegetable (GLV) intake (relative risk: 0.84 (0.74-0.94)) was inversely associated with diabetes. Subtypes of vegetables, such as root vegetables or GLVs may be beneficial for the prevention of diabetes, while total FVI may exert a weaker overall effect.

Background: In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special recommendations) on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence., Objective: We aimed to investigate whether concordance with the WCRF/AICR recommendations was related to cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study., Design: The present study included 386,355 EPIC participants from 9 European countries. At recruitment, dietary, anthropometric, and lifestyle information was collected. A score was constructed based on the WCRF/AICR recommendations on weight management, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR recommendations. The association between the score and cancer risk was estimated by using multivariable Cox regression models., Results: Concordance with the score was significantly associated with decreased risk of cancer. A 1-point increment in the score was associated with a risk reduction of 5% (95% CI: 3%, 7%) for total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%, 22%) for stomach cancer. Significant associations were also observed for cancers of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and esophagus but not for prostate, ovarian, pancreatic, and bladder cancers., Conclusion: Adherence to the WCRF/AICR recommendations for cancer prevention may lower the risk of developing most types of cancer.

Evidence from case-control studies, but less so from cohort studies, suggests a positive association between meat intake and risk of lung cancer. Therefore, this association was evaluated in the frame of the European Prospective Investigation into Cancer and Nutrition, EPIC. Data from 478,021 participants, recruited from 10 European countries, who completed a dietary questionnaire in 1992-2000 were evaluated; 1,822 incident primary lung cancer cases were included in the present evaluation. Relative risk estimates were calculated for categories of meat intake using multi-variably adjusted Cox proportional hazard models. In addition, the continuous intake variables were calibrated by means of 24-h diet recall data to account for part of the measurement error. There were no consistent associations between meat consumption and the risk of lung cancer. Neither red meat (RR = 1.06, 95% CI 0.89-1.27 per 50 g intake/day; calibrated model) nor processed meat (RR = 1.13, 95% CI 0.95-1.34 per 50 g/day; calibrated model) was significantly related to an increased risk of lung cancer. Also, consumption of white meat and fish was not associated with the risk of lung cancer. These findings do not support the hypothesis that a high intake of red and processed meat is a risk factor for lung cancer.

Background: Although several studies have investigated the association of the Mediterranean diet with overall mortality or risk of specific cancers, data on overall cancer risk are sparse., Methods: We examined the association between adherence to Mediterranean dietary pattern and overall cancer risk using data from the European Prospective Investigation Into Cancer and nutrition, a multi-centre prospective cohort study including 142,605 men and 335,873. Adherence to Mediterranean diet was examined using a score (range: 0-9) considering the combined intake of fruits and nuts, vegetables, legumes, cereals, lipids, fish, dairy products, meat products, and alcohol. Association with cancer incidence was assessed through Cox regression modelling, controlling for potential confounders., Results: In all, 9669 incident cancers in men and 21,062 in women were identified. A lower overall cancer risk was found among individuals with greater adherence to Mediterranean diet (hazard ratio=0.96, 95% CI 0.95-0.98) for a two-point increment of the Mediterranean diet score. The apparent inverse association was stronger for smoking-related cancers than for cancers not known to be related to tobacco (P (heterogeneity)=0.008). In all, 4.7% of cancers among men and 2.4% in women would be avoided in this population if study subjects had a greater adherence to Mediterranean dietary pattern., Conclusion: Greater adherence to a Mediterranean dietary pattern could reduce overall cancer risk.

Background: Previous epidemiologic studies found inconsistent results for the association between red meat intake, nitrosamines [NDMA: N-nitrosodimethylamine, and ENOC (endogenous nitroso compounds)], and the risk of bladder cancer. We investigated the association between red meat consumption, dietary nitrosamines, and heme iron and the risk of bladder cancer among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)., Methods: Data on food consumption and complete follow-up for cancer occurrence were available for a total of 481,419 participants, recruited in 10 European countries. Estimates of HRs were obtained by proportional hazard models, stratified by age at recruitment, gender, and study center and adjusted for total energy intake, smoking status, lifetime intensity of smoking, duration of smoking, educational level, and BMI., Results: After a mean follow-up of 8.7 years, 1,001 participants were diagnosed with bladder cancer. We found no overall association between intake of red meat (log2 HR: 1.06; 95% CI: 0.99-1.13), nitrosamines (log2 HR: 1.09; 95% CI: 0.92-1.30 and HR: 0.98; 95% CI: 0.92-1.05 for ENOC and NDMA, respectively) or heme iron (log2 HR: 1.05; 95 CI: 0.99-1.12) and bladder cancer risk. The associations did not vary by sex, high- versus low-risk bladder cancers, smoking status, or occupation (high vs. low risk)., Conclusions: Our findings do not support an effect of red meat intake, nitrosamines (endogenous or exogenous), or heme iron intake on bladder cancer risk., (©2011 AACR.)

Background: There is an association between a greater adherence to a Mediterranean diet and a reduced risk of developing chronic diseases. However, it is not clear whether this dietary pattern may be protective also against the development of obesity., Objective: We assessed the association between the adherence to the Mediterranean dietary pattern (MDP), prospective weight change, and the incidence of overweight or obesity., Design: We conducted a prospective cohort study [the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol Consumption, Cessation of Smoking, Eating Out of Home, and Obesity (EPIC-PANACEA) project] in 373,803 individuals (103,455 men and 270,348 women; age range: 25-70 y) from 10 European countries. Anthropometric measurements were obtained at recruitment and after a median follow-up time of 5 y. The relative Mediterranean Diet Score (rMED; score range: 0-18) was used to assess adherence to the MDP according to the consumption of 9 dietary components that are characteristic of the Mediterranean diet. The association between the rMED and 5-y weight change was modeled through multiadjusted mixed-effects linear regression., Results: Individuals with a high adherence to the MDP according to the rMED (11-18 points) showed a 5-y weight change of -0.16 kg (95% CI: -0.24, -0.07 kg) and were 10% (95% CI: 4%, 18%) less likely to develop overweight or obesity than were individuals with a low adherence to the MDP (0-6 points). The low meat content of the Mediterranean diet seemed to account for most of its positive effect against weight gain., Conclusion: This study shows that promoting the MDP as a model of healthy eating may help to prevent weight gain and the development of obesity.

Background: We investigated whether a varied consumption of vegetables and fruits is associated with lower lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study., Methods: After a mean follow-up of 8.7 years, 1,613 of 452,187 participants with complete information were diagnosed with lung cancer. Diet diversity scores (DDS) were used to quantify the variety in fruit and vegetable consumption. Multivariable proportional hazards models were used to assess the associations between DDS and lung cancer risk. All models were adjusted for smoking behavior and the total consumption of fruit and vegetables., Results: With increasing variety in vegetable subgroups, risk of lung cancer decreases [hazard ratios (HR), 0.77; 95% confidence interval (CI), 0.64-0.94 highest versus lowest quartile; P trend = 0.02]. This inverse association is restricted to current smokers (HR, 0.73; 95% CI, 0.57-0.93 highest versus lowest quartile; P trend = 0.03). In continuous analyses, in current smokers, lower risks were observed for squamous cell carcinomas with more variety in fruit and vegetable products combined (HR/two products, 0.88; 95% CI, 0.82-0.95), vegetable subgroups (HR/subgroup, 0.88; 95% CI, 0.79-0.97), vegetable products (HR/two products, 0.87; 95% CI, 0.79-0.96), and fruit products (HR/two products, 0.84; 95% CI, 0.72-0.97)., Conclusion: Variety in vegetable consumption was inversely associated with lung cancer risk among current smokers. Risk of squamous cell carcinomas was reduced with increasing variety in fruit and/or vegetable consumption, which was mainly driven by the effect in current smokers., Impact: Independent from quantity of consumption, variety in fruit and vegetable consumption may decrease lung cancer risk., ((c)2010 AACR.)

Background: Meat intake may be related to weight gain because of its high energy and fat content. Some observational studies have shown that meat consumption is positively associated with weight gain, but intervention studies have shown mixed results., Objective: Our objective was to assess the association between consumption of total meat, red meat, poultry, and processed meat and weight gain after 5 y of follow-up, on average, in the large European population who participated in the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (EPIC-PANACEA) project., Design: A total of 103,455 men and 270,348 women aged 25-70 y were recruited between 1992 and 2000 in 10 European countries. Diet was assessed at baseline with the use of country-specific validated questionnaires. A dietary calibration study was conducted in a representative subsample of the cohort. Weight and height were measured at baseline and self-reported at follow-up in most centers. Associations between energy from meat (kcal/d) and annual weight change (g/y) were assessed with the use of linear mixed models, controlled for age, sex, total energy intake, physical activity, dietary patterns, and other potential confounders., Results: Total meat consumption was positively associated with weight gain in men and women, in normal-weight and overweight subjects, and in smokers and nonsmokers. With adjustment for estimated energy intake, an increase in meat intake of 250 g/d (eg, one steak at approximately 450 kcal) would lead to a 2-kg higher weight gain after 5 y (95% CI: 1.5, 2.7 kg). Positive associations were observed for red meat, poultry, and processed meat., Conclusion: Our results suggest that a decrease in meat consumption may improve weight management.

Background: It is widely believed that cancer can be prevented by high intake of fruits and vegetables. However, inconsistent results from many studies have not been able to conclusively establish an inverse association between fruit and vegetable intake and overall cancer risk., Methods: We conducted a prospective analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to assess relationships between intake of total fruits, total vegetables, and total fruits and vegetables combined and cancer risk during 1992-2000. Detailed information on the dietary habit and lifestyle variables of the cohort was obtained. Cancer incidence and mortality data were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models. Analyses were also conducted for cancers associated with tobacco and alcohol after stratification for tobacco smoking and alcohol drinking., Results: Of the initial 142 605 men and 335 873 women included in the study, 9604 men and 21 000 women were identified with cancer after a median follow-up of 8.7 years. The crude cancer incidence rates were 7.9 per 1000 person-years in men and 7.1 per 1000 person-years in women. Associations between reduced cancer risk and increased intake of total fruits and vegetables combined and total vegetables for the entire cohort were similar (200 g/d increased intake of fruits and vegetables combined, HR = 0.97, 95% CI = 0.96 to 0.99; 100 g/d increased intake of total vegetables, HR = 0.98, 95% CI = 0.97 to 0.99); intake of fruits showed a weaker inverse association (100 g/d increased intake of total fruits, HR = 0.99, 95% CI = 0.98 to 1.00). The reduced risk of cancer associated with high vegetable intake was restricted to women (HR = 0.98, 95% CI = 0.97 to 0.99). Stratification by alcohol intake suggested a stronger reduction in risk in heavy drinkers and was confined to cancers caused by smoking and alcohol., Conclusions: A very small inverse association between intake of total fruits and vegetables and cancer risk was observed in this study. Given the small magnitude of the observed associations, caution should be applied in their interpretation.

Objective: To examine the association between fruit and vegetable consumption and risk of different histological subtypes of lung cancer among participants of the European Prospective Investigation into Cancer and Nutrition study., Methods: Multivariable Cox proportional hazard models were used to analyze the data. A calibration study in a subsample was used to reduce dietary measurement errors., Results: During a mean follow-up of 8.7 years, 1,830 incident cases of lung cancer (574 adenocarcinoma, 286 small cell, 137 large cell, 363 squamous cell, 470 other histologies) were identified. In line with our previous conclusions, we found that after calibration a 100 g/day increase in fruit and vegetables consumption was associated with a reduced lung cancer risk (HR 0.94; 95% CI 0.89-0.99). This was also seen among current smokers (HR 0.93; 95% CI 0.90-0.97). Risks of squamous cell carcinomas in current smokers were reduced for an increase of 100 g/day of fruit and vegetables combined (HR 0.85; 95% CI 0.76-0.94), while no clear effects were seen for the other histological subtypes., Conclusion: We observed inverse associations between the consumption of vegetables and fruits and risk of lung cancer without a clear effect on specific histological subtypes of lung cancer. In current smokers, consumption of vegetables and fruits may reduce lung cancer risk, in particular the risk of squamous cell carcinomas.

B vitamins and polymorphisms in genes coding for enzymes involved in one-carbon metabolism may affect DNA synthesis and methylation and thereby be implicated in carcinogenesis. Previous data on vitamins B2 and B6 and genetic polymorphisms other than those involving MTHFR as risk factors for gastric cancer (GC) are sparse and inconsistent. In this case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort, cases (n = 235) and controls (n = 601) were matched for study center, age, sex, and time of blood sampling. B2 and B6 species were measured in plasma, and the sum of riboflavin and flavin mononucleotide was used as the main exposure variable for vitamin B2 status, whereas the sum of pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid was used to define vitamin B6 status. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for GC risk were calculated with conditional logistic regression, adjusted for Helicobacter pylori infection status and smoking status. Adjusted relative risks per quartile (95% confidence interval, P(trend)) were 0.85 (0.72-1.01, 0.06) for vitamin B2 and 0.78 (0.65-0.93, <0.01) for vitamin B6. Both relations were stronger in individuals with severe chronic atrophic gastritis. The polymorphisms were not associated with GC risk and did not modify the observed vitamin-cancer associations. In summary, results from this large European cohort study showed an inverse association between vitamin B2 and GC risk, which is borderline significant, and a significant inverse association between vitamin B6 and GC risk.

Given the lack of consistent evidence of the relationship between Mediterranean dietary patterns and body fat, we assessed the cross-sectional association between adherence to a modified Mediterranean diet, BMI, and waist circumference (WC). A total of 497,308 individuals (70.7% women) aged 25-70 y from 10 European countries participated in this study. Diet was assessed at baseline using detailed validated country-specific questionnaires, and anthropometrical measurements were collected using standardized procedures. The association between the degree of adherence to the modified-Mediterranean Diet Score (mMDS) (including high consumption of vegetables, legumes, fruits and nuts, cereals, fish and seafood, and unsaturated:saturated fatty acids ratio; moderate alcohol intake; and low consumption of meat and meat products and dairy products) and BMI (kg.m(-2)) or WC (cm) was modeled through mixed-effects linear regression, controlling for potential confounders. Overall, the mMDS was not significantly associated with BMI. Higher adherence to the Mediterranean diet was significantly associated with lower WC, for a given BMI, in both men (-0.09; 95% CI -0.14 to -0.04) and women (-0.06; 95% CI -0.10 to -0.01). The association was stronger in men (-0.20; 95% CI -0.23 to -0.17) and women (-0.17; 95% CI -0.21 to -0.13) from Northern European countries. Despite the observed heterogeneity among regions, results of this study suggest that adherence to a modified Mediterranean diet, high in foods of vegetable origin and unsaturated fatty acids, is associated with lower abdominal adiposity measured by WC in European men and women.

Background: Studies in many countries have reported higher lung cancer incidence and mortality in individuals with lower socioeconomic status., Methods: To investigate the role of smoking in these inequalities, we used data from 391,251 participants in the European Prospective Investigation into Cancer and Nutrition study, a cohort of individuals in 10 European countries. We collected information on smoking (history and quantity), fruit and vegetable consumption, and education through questionnaires at study entry and gathered data on lung cancer incidence for a mean of 8.4 years. Socioeconomic status was defined as the highest attained level of education, and participants were grouped by sex and region of residence (Northern Europe, Germany, or Southern Europe). Relative indices of inequality (RIIs) of lung cancer risk unadjusted and adjusted for smoking were estimated using Cox regression models. Additional analyses were performed by histological type., Results: During the study period, 939 men and 692 women developed lung cancer. Inequalities in lung cancer risk (RII(men) = 3.62, 95% confidence interval [CI] = 2.77 to 4.73, 117 vs 52 per 100,000 person-years for lowest vs highest education level; RII(women) = 2.39, 95% CI = 1.77 to 3.21, 46 vs 25 per 100,000 person-years) decreased after adjustment for smoking but remained statistically significant (RII(men) = 2.29, 95% CI = 1.75 to 3.01; RII(women) = 1.59, 95% CI = 1.18 to 2.13). Large RIIs were observed among men and women in Northern European countries and among men in Germany, but inequalities in lung cancer risk were reverse (RIIs < 1) among women in Southern European countries. Inequalities differed by histological type. Adjustment for smoking reduced inequalities similarly for all histological types and among men and women in all regions. In all analysis, further adjustment for fruit and vegetable consumption did not change the estimates., Conclusion: Self-reported smoking consistently explains approximately 50% of the inequalities in lung cancer risk due to differences in education.

The NORMTOX model predicts the lifetime-averaged exposure to contaminants through multiple environmental media, that is, food, air, soil, drinking and surface water. The model was developed to test the coherence of Dutch environmental quality objectives (EQOs). A set of EQOs is called coherent if simultaneous exposure to different environmental media that are all polluted up to their respective EQOs does not result in exceeding the acceptable or tolerable daily intake (ADI or TDI). Aim of the present study is to separate the impact of uncertainty and interindividual variability in coherence predictions with the NORMTOX model. The method is illustrated in a case study for chlorfenvinphos, mercury and nitrate. First, ANOVA was used to calculate interindividual variability in input parameters. Second, nested Monte Carlo simulation was used to propagate uncertainty and interindividual variability separately. Lifetime-averaged exposure to chlorfenvinphos, mercury and nitrate was modeled for the Dutch population. Output distributions specified the population fraction at risk, due to a particular exposure, and the reliability of this risk. From the case study, it was obtained that at lifelong exposure to all media polluted up to their standard, 100% of the Dutch population exceeds the ADI for chlorfenvinphos, 15% for mercury and 0% for nitrate. Variance in exposure to chlorfenvinphos, mercury and nitrate is mostly caused by interindividual variability instead of true uncertainty. It is concluded that the likelihood that ADIs of chlorfenvinphos and mercury will be exceeded should be further explored. If exceeding is likely, decision makers should focus on identification of high-risk subpopulations, rather than on additional research to obtain more accurate estimates for particular parameters.

Previous studies have shown inconsistent associations of folate intake and polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene with gastric cancer risk. Our nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort is the first prospective study of blood folate levels and gastric cancer. Gastric cancer cases (n=247) and controls (n=631) were matched for study center, age, sex, and time of blood donation. Two common single nucleotide polymorphisms of the MTHFR gene were determined, as were plasma concentrations of folate, cobalamin (vitamin B12), total homocysteine, and methylmalonic acid (cobalamin deficiency marker) in prediagnostic plasma. Risk measures were calculated with conditional logistic regression. Although no relations were observed between plasma folate or total homocysteine concentrations and gastric cancer, we observed a trend toward lower risk of gastric cancer with increasing cobalamin concentrations (odds ratio, 0.79 per SD increase in cobalamin; P=0.01). Further analyses showed that the inverse association between cobalamin and gastric cancer was confined to cancer cases with low pepsinogen A levels (marker of severe chronic atrophic gastritis) at the time of blood sampling. The 677 C-->T MTHFR polymorphism was not associated with gastric cancer, but we observed an increased risk with the variant genotype of the 1298 A-->C polymorphism (odds ratio, 1.47 for CC versus AA; P=0.04). In conclusion, we found no evidence of a role of folate in gastric cancer etiology. However, we observed increased gastric cancer risk at low cobalamin levels that was most likely due to compromised cobalamin status in atrophic gastritis preceding gastric cancer.

Objective: Most studies on tobacco smoking have focused on daily-smokers. Occasional smokers, who have never smoked daily, have often been included in the reference group of never-smokers. We have investigated the association between occasional smoking and cancer of the bladder, kidney, pancreas, upper aero-digestive tract and lung., Methods: The study population consisted of 158,488 persons, who provided information on occasional smoking, within the European Prospective Investigation into Cancer and Nutrition (EPIC), 780 of whom developed a smoking-related cancer. We used Cox proportional hazard model, stratified by gender and country to estimate incidence rate ratios (IRR) for smoking-related cancers., Results: The results suggest that occasional smokers have a higher risk of bladder cancer (IRR: 1.92, 95% confidence interval (CI) 0.93-3.98) and of the major smoking-related cancers combined (IRR: 1.24, 95% CI 0.80-1.94) than true never-smokers. Including occasional smokers in the reference group resulted in a lower risk estimate for former and current smokers., Conclusions: Occasional smoking should be discouraged.

Within the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors examined the association of ethanol intake at recruitment (1,119 cases) and mean lifelong ethanol intake (887 cases) with lung cancer. Information on baseline and past alcohol consumption, lifetime tobacco smoking, diet, and the anthropometric characteristics of 478,590 participants was collected between 1992 and 2000. Cox proportional hazards regression was used to calculate multivariate-adjusted hazard ratios and 95% confidence intervals. Overall, neither ethanol intake at recruitment nor mean lifelong ethanol intake was significantly associated with lung cancer. However, moderate intake (5-14.9 g/day) at recruitment (hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.63, 0.90) and moderate mean lifelong intake (HR = 0.80, 95% CI: 0.66, 0.97) were associated with a lower lung cancer risk in comparison with low consumption (0.1-4.9 g/day). Compared with low intake, a high (> or =60 g/day) mean lifelong ethanol intake tended to be related to a higher risk of lung cancer (HR = 1.29, 95% CI: 0.93, 1.74), but high intake at recruitment was not. Although there was no overall association between ethanol intake and risk of lung cancer, the authors cannot rule out a lower risk for moderate consumption and a possibly increased risk for high lifelong consumption.

Vitamin C is an antioxidant and inhibitor of carcinogenic N-nitroso compound production in the stomach. Higher dietary vitamin C consumption is associated with decreased risk of gastric cancer (GC) in numerous case-control studies, but data from prospective studies are limited, particularly so for blood measures of vitamin C. The objective of this study was to determine the association of plasma and dietary vitamin C levels with the risk of GC in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 European countries. Using a fluorometric method, vitamin C was measured in pre-diagnostic plasma from 215 GC cases (matched controls = 416). Conditional logistic regression models adjusted by body mass index, total energy intake, smoking status/duration/intensity and Helicobacter pylori infection status were used to estimate relative cancer risks. No association with GC risk was observed for dietary vitamin C, whereas an inverse GC risk was observed in the highest versus lowest quartile of plasma vitamin C [odds ratio (OR) = 0.55, 95% confidence interval (CI) = 0.31-0.97, P(trend) = 0.043], which was maintained after exclusion of cases with

Epidemiologic studies suggest that a high intake of fruits and vegetables is associated with decreased risk of cancers of the upper aero-digestive tract. We studied data from 345,904 subjects of the prospective European Investigation into Cancer and Nutrition (EPIC) recruited in seven European countries, who had completed a dietary questionnaire in 1992-1998. During 2,182,560 person years of observation 352 histologically verified incident squamous cell cancer (SCC) cases (255 males; 97 females) of the oral cavity, pharynx, larynx, and esophagus were identified. Linear and restricted cubic spline Cox regressions were fitted on variables of intake of fruits and vegetables and adjusted for potential confounders. We observed a significant inverse association with combined total fruits and vegetables intake (estimated relative risk (RR) = 0.91; 95% confidence interval (95% CI) 0.83-1.00 per 80 g/d of consumption), and nearly significant inverse associations in separate analyses with total fruits and total vegetables intake (RR: 0.97 (95% CI: 0.92-1.02) and RR = 0.89 (95% CI: 0.78-1.02) per 40 g/d of consumption). Overall, vegetable subgroups were not related to risk with the exception of intake of root vegetables in men. Restricted cubic spline regression did not improve the linear model fits except for total fruits and vegetables and total fruits with a significant decrease in risk at low intake levels (<120 g/d) for fruits. Dietary recommendations should consider the potential benefit of increasing fruits and vegetables consumption for reducing the risk of cancers of the upper aero-digestive tract, particularly at low intake.

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.