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Background: Conventional dietary assessment methods are affected by measurement errors. We developed a smartphone-based 2-h recall (2hR) methodology to reduce participant burden and memory-related bias. Objective: Assessing the validity of the 2hR method against traditional 24-h recalls (24hRs) and objective biomarkers. Methods: Dietary intake was assessed in 215 Dutch adults on 6 randomly selected nonconsecutive days (i.e., 3 2hR-days and 3 24hRs) during a 4-wk period. Sixty-three participants provided 4 24-h urine samples, to assess urinary nitrogen and potassium concentrations. Results: Intake estimates of energy (2052±503 kcal vs. 1976±483 kcal) and nutrients (e.g., protein: 78±23 g vs. 71±19 g; fat: 84±30 g vs. 79±26 g; carbohydrates: 220±60 g vs. 216±60 g) were slightly higher with 2hR-days than with 24hRs. Comparing self-reported protein and potassium intake to urinary nitrogen and potassium concentrations indicated a slightly higher accuracy of 2hR-days than 24hRs (protein: −14% vs. −18%; potassium: −11% vs. −16%). Correlation coefficients between methods ranged from 0.41 to 0.75 for energy and macronutrients and from 0.41 to 0.62 for micronutrients. Generally, regularly consumed food groups showed small differences in intake (0.60). Intake of energy, nutrients, and food groups showed similar reproducibility (intraclass correlation coefficient) for 2hR-days and 24hRs. Conclusions: Comparing 2hR-days with 24hRs showed a relatively similar group-level bias for energy, most nutrients, and food groups. Differences were mostly due to higher intake estimates by 2hR-days. Biomarker comparisons showed less underestimation by 2hR-days as compared with 24hRs, suggesting that 2hR-days are a valid approach to assess the intake of energy, nutrients, and food groups. This trial was registered at the Dutch Central Committee on Research Involving Human Subjects (CCMO) registry as ABR. No. NL69065.081.19.

Microbiome data are characterized by several aspects that make them challenging to analyse statistically: they are compositional, high dimensional and rich in zeros. A large array of statistical methods exist to analyse these data. Some are borrowed from other fields, such as ecology or RNA-sequencing, while others are custom-made for microbiome data. The large range of available methods, and which is continuously expanding, means that researchers have to invest considerable effort in choosing what method(s) to apply. In this paper we list 14 statistical methods or approaches that we think should be generally avoided. In several cases this is because we believe the assumptions behind the method are unlikely to be met for microbiome data. In other cases we see methods that are used in ways they are not intended to be used. We believe researchers would be helped by more critical evaluations of existing methods, as not all methods in use are suitable or have been sufficiently reviewed. We hope this paper contributes to a critical discussion on what methods are appropriate to use in the analysis of microbiome data.

Introduction: Postoperative complications impact morbidity and mortality of colon cancer patients. Emerging evidence suggests that intestinal microbiota might play a critical role in the development of postoperative complications after gastrointestinal surgery. Here, we studied changes in fecal microbiota composition comparing samples collected before and after colon cancer surgery. Moreover, we examined whether the microbiota composition before surgery was associated with postoperative complications, and we explored potential determinants of the preoperative microbiota in colon cancer patients. Methods: For this study, two fecal samples were provided by 78 patients with colon cancer. The first (preoperative) sample was collected shortly after diagnosis and before (median and interquartile (IQR) range of 4 (2-6) days) colon cancer surgery. The second (postoperative) sample was collected approximately 6 weeks (median and IQR of 42 (37-47) days) after surgery and before start of adjuvant chemotherapy (whenever applicable). Based on 16S ribosomal RNA gene amplicon sequencing, the fecal microbiota diversity and composition were determined. Preoperative microbiota composition of patients who developed postoperative complications in the 30 days following surgery (n=18, 23%) was compared to those who did not (n=60, 77%) using univariate and multivariate analyses. Explorative random forest analyses were conducted to identify predictors of complication status, with relative abundance of the core genera, sex, age, fecal calprotectin levels, dietary fiber intake, body mass index, smoking status, ASA classification, cancer stage and tumor location being considered as potential predictors. Results: After surgery, microbial alpha diversity was reduced compared to the preoperative situation, whereas compositional changes over time only reached statistical significance for Lachnospiraceae NK4A136 and Coprococcus 1, which both decreased in relative abundance after surgery. Already before the start of surgery, relative abundance of the genera Bacteroides (10% vs 6%) and Lachnoclostridium (0.6% vs 0.2%) appeared to be higher in patients with complications versus those with uncomplicated recovery. In a prediction analysis, current smoking and relative abundance of Lachnoclostridium were identified as most profound predictors of complication status. Fecal calprotectin levels and current smoking status explained most (together 6%) of the overall variation in microbiota composition before surgery. Conclusion: In this study, higher relative abundances of the genera Bacteroides and Lachnoclostridium before surgery were associated with postoperative complications in patients with colon cancer. Future studies should expand on the potential causal and pathogenic routes underlying these observations. Citation Format: Dieuwertje E. Kok, Jannigje G. Kers, Hendriek C. Boshuizen, Niels Klaassen, Henk K. van Halteren, Flip M. Kruyt, Marjolein L. Smidt, Johannes H. De Wilt, Annemarie Boleij, Ellen Kampman, Erwin G. Zoetendal. Pre- and postoperative fecal microbiota and its association with complications after surgery in colon cancer patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4380.

Background: Studies do not show consistent relationships between self-reported intake of sugar and outcome of disease. To overcome the drawbacks of self-reported intake methods, we investigated whether there is an agreement in ranking of individuals between their self-reported sugar intake and urinary sucrose and fructose. Methods: We used data of 198 Dutch adults (106 women) from the DUPLO study. Sugar intake of all foods and drinks consumed over 24-hour period was estimated by collecting duplicate portions (DP) and 24-hour recalls (24hR), telephone (24hRT) and Web-based (24hRW), while sugar excretion was based on 24-hour urine samples. Sugar content of 24hR was calculated using a newly developed sugar database and sugar content of DPs and urine samples was calculated using high-performance liquid chromatography–atomic emission spectrometry and LC/MS-MS, respectively. Measurement error models assessed validity coefficients (VC) and attenuation factors (AF). Coefficients were compared with those of protein biomarker. Results: The VC for the marker, using DP as reference, showed comparability with substantially better ranking of participants (0.72 for women and 0.93 for men), than 24hRT (0.57 and 0.78) or 24hRW (0.70 and 0.78) as reference in the sucrose models. The VC of the sucrose models was within 10% of the protein models, except for the model with 24hRT as reference, among women. The AF started at higher values and increased by a greater factor compared with the VC. Conclusions: Repeated measurements of urinary sucrose and fructose as a marker of daily sucrose intake had a ranking performance comparable to urinary nitrogen as marker of protein intake in free-living Dutch adults. Impact: The validation of the sugar biomarker in a free-living population with three different dietary assessment methods and its comparable ranking ability with a good recovery biomarker (i.e., protein biomarker) have important research applications. The biomarker may be used for validating dietary assessment methods, for monitoring compliance in human feeding studies, for monitoring the effect of public health interventions, and as a surrogate for ranking subjects according to sucrose intake when information on sucrose in food composition databases is lacking.

Background An unhealthy lifestyle is associated with the risk of colorectal cancer (CRC), but it is unclear whether overall lifestyle after a CRC diagnosis is associated with risks of recurrence and mortality. Objectives To examine associations between postdiagnosis lifestyle and changes in lifestyle after a CRC diagnosis with risks of CRC recurrence and all-cause mortality. Methods The study population included 1425 newly diagnosed, stage I–III CRC patients from 2 prospective cohort studies enrolled between 2010 and 2016. Lifestyle, including BMI, physical activity, diet, and alcohol intake, was assessed at diagnosis and at 6 months postdiagnosis. We assigned lifestyle scores based on concordance with 2 sets of cancer prevention guidelines—from the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) and the American Cancer Society (ACS)—and national disease prevention guidelines. Higher scores indicate healthier lifestyles. We computed adjusted HRs and 95% CIs using Cox regression. Results We observed 164 recurrences during a 2.8-year median follow-up and 171 deaths during a 4.4-year median follow-up. No associations were observed for CRC recurrence. A lifestyle more consistent with the ACS recommendations was associated with a lower all-cause mortality risk (HR per +1 SD, 0.85; 95% CI: 0.73–0.995). The same tendency was observed for higher WCRF/AICR (HR, 0.92; 95% CI: 0.78–1.08) and national (HR, 0.90; 95% CI: 0.77–1.05) lifestyle scores, although these associations were statistically nonsignificant. Generally, no statistically significant associations were observed for BMI, physical activity, diet, or alcohol. Improving one's lifestyle after diagnosis (+1 SD) was associated with a lower all-cause mortality risk for the ACS (HR, 0.80; 95% CI: 0.67–0.96) and national (HR, 0.84; 95% CI: 0.70–0.999) scores, yet was statistically nonsignificant for the WCRF/AICR score (HR, 0.94; 95% CI: 0.78–1.13). Conclusions A healthy lifestyle after CRC diagnosis and improvements therein were not associated with the risk of CRC recurrence, but were associated with a decreased all-cause mortality risk.

Background: The associations of abdominal skeletal muscle mass index (SMI), visceral and subcutaneous adipose tissue (VAT and SAT, respectively), and mortality among patients with stage I–III colorectal cancer may differ for men and women, but only few studies stratified their data into men and women. We investigated associations of abdominal SMI, VAT, and SAT with overall mortality among men and among women with stage I–III colorectal cancer. Methods: SMI, VAT, and SAT were assessed from abdominal CT images for 1,998 patients with stage I–III colorectal cancer diagnosed between 2006 and 2015. Restricted cubic splines (RCS) were used to investigate associations of SMI, VAT, and SAT with overall mortality. Results: Average age of the participants was 67.9 ± 10.6 years and 58% were men. During a median follow-up of 4.3 years, 546 (27%) patients died. Among men, the association of SMI and mortality was statistically significant in a nonlinear way in the RCS analyses, with lower SMI levels associated with higher mortality. SMI was not associated with mortality among women. SAT was associated with mortality in a nonlinear way for men and for women, with lower SAT levels being associated with higher mortality. VAT was not significantly associated with mortality in men or women. Conclusion: Associations of abdominal skeletal muscle mass with mortality among patients with colorectal cancer were not the same for men and for women. Impact: This study stresses the importance for more attention on sex-related differences in body composition and cancer outcomes.

Background Food frequency questionnaires (FFQs) are a commonly used method to assess dietary intake in epidemiological studies. It is important to evaluate the validity of FFQs in the population of interest.Objective To evaluate the validity of an FFQ for measuring dietary intake in survivors of colorectal cancer (CRC), relative to a 7-day dietary record.Design Dietary intake was assessed 1 year after the end of CRC treatment. Participants first completed a 7-day dietary record and 2 weeks later a 253-item FFQ that measured intake in the preceding month.Participants/setting Data were used from a subsample of participants (n=100) enrolled in an ongoing prospective study (EnCoRe study) in the Netherlands, from 2015 to 2018.Main outcome measures Estimated intakes of total energy, 19 nutrients, and 20 food groups as well as scoring adherence to the dietary recommendations of the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) were compared between both dietary assessment methods.Statistical analyses performed Means and standard deviations, Spearman rank correlations corrected for within-person variation and total energy, and kappa agreement between quintiles were assessed.Results The median Spearman correlation corrected for within-person variation for nutrients and total energy was 0.60. Correlations >0.50 were found for 15 of 19 nutrients, with highest agreement for vitamin B-12 (0.74), polysaccharides (0.75), and alcohol (0.91). On average, 73% (range=60% to 84%) of participants were classified into the exact same or adjacent nutrient quintile. The median Spearman correlation corrected for within-person variation for food groups was 0.62. Correlations >0.50 were found for 17 of 20 food groups, with highest agreement for cereals and cereal products (0.96), fish (0.96), and potatoes (0.99). The Spearman correlation between total scores of the WCRF/AICR dietary recommendations was 0.53.Conclusions Relative to a 7-day dietary record, the validity of an FFQ for measuring dietary intake among survivors of CRC appeared moderate to good for most nutrients and food groups.

Background: Despite the established relation between energy restriction (ER) and metabolic health, the most beneficial nutrient composition of a weight-loss diet is still a subject of debate. Objectives: The aim of the study was to examine the additional effects of nutrient quality on top of ER. Methods: A parallel-designed, 12-week 25% ER dietary intervention study was conducted (clinicaltrials.gov: NCT02194504). Participants aged 40-70 years with abdominal obesity were randomized over 3 groups: a 25% ER high-nutrient-quality diet (n = 40); a 25% ER low-nutrient-quality diet (n = 40); or a habitual diet (n = 30). Both ER diets were nutritionally adequate, and the high-nutrient-quality ER diet was enriched in MUFAs, n-3 PUFAs, fiber, and plant protein and reduced in fructose. Before and after the intervention, intrahepatic lipids, body fat distribution, fasting and postprandial responses to a mixed-meal shake challenge test of cardiometabolic risk factors, lipoproteins, vascular measurements, and adipose tissue transcriptome were assessed. Results: The high-nutrient-quality ER diet (-8.4 ± 3.2) induced 2.1 kg more weight loss (P = 0.007) than the low-nutrient-quality ER diet (-6.3 ± 3.9), reduced fasting serum total cholesterol (P = 0.014) and plasma triglycerides (P < 0.001), promoted an antiatherogenic lipoprotein profile, and induced a more pronounced decrease in adipose tissue gene expression of energy metabolism pathways than the low-quality ER diet. Explorative analyses showed that the difference in weight loss between the two ER diets was specifically present in insulin-sensitive subjects (HOMA-IR ≤ 2.5), in whom the high-nutrient-quality diet induced 3.9 kg more weight loss than the low-nutrient-quality diet. Conclusions: A high-nutrient-quality 25% ER diet is more beneficial for cardiometabolic health than a low-nutrient-quality 25% ER diet. Overweight, insulin-sensitive subjects may benefit more from a high- than a low-nutrient-quality ER diet with respect to weight loss, due to potential attenuation of glucose-induced lipid synthesis in adipose tissue.

Objective:To illustrate the impact of combining 24 h recall (24hR) and FFQ estimates using regression calibration (RC) and enhanced regression calibration (ERC) on diet–disease associations.Setting:Wageningen area, the Netherlands, 2011–2013.Design:Five approaches for obtaining self-reported dietary intake estimates of protein and K were compared: (i) uncorrected FFQ intakes (FFQ); (ii) uncorrected average of two 24hR ( $\overline {\rm R}$ ); (iii) average of FFQ and $\overline {\rm R}$ ( ${\overline {\rm F}}\,\overline {\rm R}}$ ); (iv) RC from regression of 24hR v. FFQ; and (v) ERC by adding individual random effects to the RC approach. Empirical attenuation factors (AF) were derived by regression of urinary biomarker measurements v. the resulting intake estimates.Participants:Data of 236 individuals collected within the National Dietary Assessment Reference Database.Results:Both FFQ and 24hR dietary intake estimates were measured with substantial error. Using statistical techniques to correct for measurement error (i.e. RC and ERC) reduced bias in diet–disease associations as indicated by their AF approaching 1 (RC 1·14, ERC 0·95 for protein; RC 1·28, ERC 1·34 for K). The larger sd and narrower 95% CI of AF obtained with ERC compared with RC indicated that using ERC has more power than using RC. However, the difference in AF between RC and ERC was not statistically significant, indicating no significantly better de-attenuation by using ERC compared with RC. AF larger than 1, observed for the ERC for K, indicated possible overcorrection.Conclusions:Our study highlights the potential of combining FFQ and 24hR data. Using RC and ERC resulted in less biased associations for protein and K.

No association between polymorphisms in CYP2E1, GSTM1, NAT1, NAT2 and the risk of gastric adenocarcinoma in the European prospective investigation into cancer and nutrition.

Simple Summary Current lifestyle recommendations for cancer survivors are the same as those for the general public to decrease their risk of cancer. However, it is unclear what kind of lifestyle behaviors are important for prognosis after a cancer diagnosis. In an observational study among 1180 colorectal cancer patients, we aimed to identify which lifestyle behaviors were most important regarding cancer recurrence and all-cause mortality. We simultaneously evaluated lifestyle behaviors, related to diet, physical activity, adiposity, alcohol use, and smoking. Higher intakes of sugary drinks were associated with increased recurrence risk. For all-cause mortality, fruit and vegetable, liquid fat and oil, and animal protein intake were identified as important lifestyle behaviors. Our exploratory findings identified several lifestyle behaviors related to prognosis after colorectal cancer. These findings should be confirmed in other observational studies before they can be translated into clinical practice. Abstract Current lifestyle recommendations for cancer survivors are the same as those for the general public to decrease their risk of cancer. However, it is unclear which lifestyle behaviors are most important for prognosis. We aimed to identify which lifestyle behaviors were most important regarding colorectal cancer (CRC) recurrence and all-cause mortality with a data-driven method. The study consisted of 1180 newly diagnosed stage I–III CRC patients from a prospective cohort study. Lifestyle behaviors included in the current recommendations, as well as additional lifestyle behaviors related to diet, physical activity, adiposity, alcohol use, and smoking were assessed six months after diagnosis. These behaviors were simultaneously analyzed as potential predictors of recurrence or all-cause mortality with Random Survival Forests (RSFs). We observed 148 recurrences during 2.6-year median follow-up and 152 deaths during 4.8-year median follow-up. Higher intakes of sugary drinks were associated with increased recurrence risk. For all-cause mortality, fruit and vegetable, liquid fat and oil, and animal protein intake were identified as the most important lifestyle behaviors. These behaviors showed non-linear associations with all-cause mortality. Our exploratory RSF findings give new ideas on potential associations between certain lifestyle behaviors and CRC prognosis that still need to be confirmed in other cohorts of CRC survivors.

Vaccination has reduced the disease burden of vaccine-preventable diseases. However, the extent to which seasonal cycles of immunity could influence vaccine-induced immunity is not well understood. A national cross-sectional serosurveillance study performed in the Netherlands (Pienter-2) yielded data to investigate whether season of vaccination was associated with antibody responses induced by DT-IPV (diphtheria, tetanus and poliomyelitis), MMR (measles, mumps and rubella) and meningococcus C (MenC) vaccines in children. In total, 434 children met the inclusion criteria to study DT-IPV immunity, 811 for MMR and 311 for MenC. Differences in log(antibody levels) by season of vaccination were investigated with linear multivariable regression analyses. Seroconversion rates varied according to season of vaccination for rubella (90% of autumn-vaccinated childrenvs.99% of winter-vaccinated had concentrations above cut-off levels). Summer-vaccinated boys showed a slower decline of tetanus antibodies (6% per month), in comparison with winter-vaccinated boys. In conclusion, season of vaccination showed little association with immunological protection. However, a number of associations were seen with aP-value of about 0.03; and adding data from a just-completed nationwide serological study might add more power to the current study. Further immunological and longitudinal investigations could help understand the mechanisms of seasonal influence in vaccine-induced responses.

Objectives We investigated the potential impact of reduced tobacco use scenarios on total life expectancy and health expectancies, i.e., healthy life years and unhealthy life years. Methods Data from the Belgian Health Interview Survey 2013 were used to estimate smoking and disability prevalence. Disability was based on the Global Activity Limitation Indicator. We used DYNAMO-HIA to quantify the impacts of risk factor changes and to compare the “business-as-usual” with alternative scenarios. Results The “business-as-usual” scenario estimated that in 2028 the 15-year-old men/women would live additional 50/52 years without disability and 14/17 years with disability. The “smoking-free population” scenario added 3.4/2.8 healthy life years and reduced unhealthy life years by 0.79/1.9. Scenarios combining the prevention of smoking initiation with smoking cessation programs are the most effective, yielding the largest increase in healthy life years (1.9/1.7) and the largest decrease in unhealthy life years (− 0.80/− 1.47). Conclusions Health impact assessment tools provide different scenarios for evidence-informed public health actions. New anti-smoking strategies or stricter enforcement of existing policies potentially gain more healthy life years and reduce unhealthy life years in Belgium.

Purpose: Previous studies have shown that > 50% of colorectal cancer (CRC) patients treated with adjuvant chemotherapy gain weight after diagnosis. This may affect long-term health. Therefore, prevention of weight gain has been incorporated in oncological guidelines for CRC with a focus on patients that undergo adjuvant chemotherapy treatment. It is, however, unknown how changes in weight after diagnosis relate to weight before diagnosis and whether weight changes from pre-to-post diagnosis are restricted to chemotherapy treatment. We therefore examined pre-to-post diagnosis weight trajectories and compared them between those treated with and without adjuvant chemotherapy. Methods: We included 1184 patients diagnosed with stages I–III CRC between 2010 and 2015 from an ongoing observational prospective study. At diagnosis, patients reported current weight and usual weight 2 years before diagnosis. In the 2 years following diagnosis, weight was self-reported repeatedly. We used linear mixed models to analyse weight trajectories. Results: Mean pre-to-post diagnosis weight change was −0.8 (95% CI −1.1, −0.4) kg. Post-diagnosis weight gain was + 3.5 (95% CI 2.7, 4.3) kg in patients who had lost ≥ 5% weight before diagnosis, while on average clinically relevant weight gain after diagnosis was absent in the groups without pre-diagnosis weight loss. Pre-to-post diagnosis weight change was similar in patients treated with (−0.1 kg (95%CI −0.8, 0.6)) and without adjuvant chemotherapy (−0.9 kg (95%CI −1.4, −0.5)). Conclusions: Overall, hardly any pre-to-post diagnosis weight change was observed among CRC patients, because post-diagnosis weight gain was mainly observed in patients who lost weight before diagnosis. This was observed independent of treatment with adjuvant chemotherapy.

It is suggested that nutrient densities are less affected by measurement errors than absolute intake estimates of dietary exposure. We compared the validity of absolute intakes and densities of protein (kJ from protein/total energy (kJ)), potassium, and sodium (potassium or sodium (in mg)/total energy (kJ)) assessed by different dietary assessment methods. For 69 Dutch subjects, two duplicate portions (DPs), five to fifteen 24-h dietary recalls (24 hRs, telephone-based and web-based) and two food frequency questionnaires (FFQs) were collected and compared to duplicate urinary biomarkers and one or two doubly labelled water measurements. Multivariate measurement error models were used to estimate validity coefficients (VCs) and attenuation factors (AFs). This research showed that group bias diminished for protein and sodium densities assessed by all methods as compared to the respective absolute intakes, but not for those of potassium. However, the VCs and AFs for the nutrient densities did not improve compared to absolute intakes for all four methods, except for the AF of sodium density (0.71) or the FFQ which was better than that of the absolute sodium intake (0.51). Thus, using nutrient densities rather than absolute intakes does not necessarily improve the performance of the DP, FFQ, or 24 hR.

In most countries, non-communicable diseases have taken over infectious diseases as the most important causes of death. Many non-communicable diseases that were previously lethal diseases have become chronic, and this has changed the healthcare landscape in terms of treatment and prevention options. Currently, a large part of healthcare spending is targeted at curing and caring for the elderly, who have multiple chronic diseases. In this context prevention plays an important role, as there are many risk factors amenable to prevention policies that are related to multiple chronic diseases. This article discusses the use of simulation modeling to better understand the relations between chronic diseases and their risk factors with the aim to inform health policy. Simulation modeling sheds light on important policy questions related to population aging and priority setting. The focus is on the modeling of multiple chronic diseases in the general population and how to consistently model the relations between chronic diseases and their risk factors by combining various data sources. Methodological issues in chronic disease modeling and how these relate to the availability of data are discussed. Here, a distinction is made between (a) issues related to the construction of the epidemiological simulation model and (b) issues related to linking outcomes of the epidemiological simulation model to economic relevant outcomes such as quality of life, healthcare spending and labor market participation. Based on this distinction, several simulation models are discussed that link risk factors to multiple chronic diseases in order to explore how these issues are handled in practice. Recommendations for future research are provided.

Background Prevention aiming at smoking, alcohol consumption, and BMI could potentially bring large gains in life expectancy (LE) and health expectancy measures such as Healthy Life Years (HLY) and Life Expectancy in Good Perceived Health (LEGPH) in the European Union. However, the potential gains might differ by region. Methods A Sullivan life table model was applied for 27 European countries to calculate the impact of alternative scenarios of lifestyle behavior on life and health expectancy. Results were then pooled over countries to present the potential gains in HLY and LEGPH for four European regions. Results Simulations show that up to 4 years of extra health expectancy can be gained by getting all countries to the healthiest levels of lifestyle observed in EU countries. This is more than the 2 years to be gained in life expectancy. Generally, Eastern Europe has the lowest LE, HLY, and LEGPH. Even though the largest gains in LEPGH and HLY can also be made in Eastern Europe, the gap in LE, HLY, and LEGPH can only in a small part be closed by changing smoking, alcohol consumption, and BMI. Conclusion Based on the current data, up to 4 years of good health could be gained by adopting lifestyle as seen in the best-performing countries. Only a part of the lagging health expectancy of Eastern Europe can potentially be solved by improvements in lifestyle involving smoking and BMI. Before it is definitely concluded that lifestyle policy for alcohol use is of relatively little importance compared to smoking or BMI, as our findings suggest, better data should be gathered in all European countries concerning alcohol use and the odds ratios of overconsumption of alcohol. Electronic supplementary material The online version of this article (10.1186/s12963-018-0181-5) contains supplementary material, which is available to authorized users.

Objective: Patients with rheumatoid arthritis (RA) have a significantly increased risk of mortality compared with the general population. One of the most important predictors for mortality is somatic comorbidity. Moreover, studies have demonstrated that comorbid depression is associated with mortality. Which specific comorbidities are associated with mortality is less investigated. The purpose of this study was to investigate the association of a wide range of comorbidities with mortality in patients with RA. Methods: Longitudinal data over a 14-year period were collected from 882 patients with RA. Data were assessed with questionnaires. The mortality status was obtained from the Statistics Netherlands for the period 1996–2011 for 99% of the patients. Somatic comorbidity was assessed in 1997, 1998, 1999, and 2008 and measured by a national population-based questionnaire including 20 chronic diseases. Comorbid depression was assessed in 1997, 1998, and 1999 and measured with the Center for Epidemiologic Studies Depression Scale. Cox regression was used to study the relationship between comorbidity and mortality. Results: At baseline, 72% of the patients were women. The mean ± SD age was 59.3 ± 14.8 years, and the median (interquartile range) disease duration was 5.0 (2.0–14.0) years. A total of 345 patients died during the study period. Comorbidities that were associated with mortality were circulatory conditions (hazard ratio [HR] 1.60 [95% confidence interval (95% CI) 1.15–2.22]), respiratory conditions (HR 1.43 [95% CI 1.09–1.89]), cancer (HR 2.00 [95% CI 1.28–3.12]), and depression (HR 1.35 [95% CI 1.06–1.72]). Conclusion: Comorbid circulatory conditions, respiratory conditions, cancer, and depression are associated with mortality among patients with RA. Careful monitoring of these comorbidities during the course of the disease and adequate referral may improve health outcomes and chances of surviving.

Background: The “meeting-in-the-middle” (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case–control study of hepatocellular carcinoma (HCC) within European Prospective Investigation into Cancer and Nutrition (EPIC), where healthy lifestyle index (HLI) variables were related to targeted serum metabolites. Methods: Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls. Partial least squares analysis related 7 lifestyle variables from a modified HLI to a set of 132 serum-measured metabolites and a liver function score. Mediation analysis evaluated whether metabolic profiles mediated the relationship between each lifestyle exposure and HCC risk. Results: Exposure-related metabolic signatures were identified. Particularly, the body mass index (BMI)-associated metabolic component was positively related to glutamic acid, tyrosine, PC aaC38:3, and liver function score and negatively to lysoPC aC17:0 and aC18:2. The lifetime alcohol-specific signature had negative loadings on sphingomyelins (SM C16:1, C18:1, SM(OH) C14:1, C16:1 and C22:2). Both exposures were associated with increased HCC with total effects (TE) = 1.23 (95% confidence interval = 0.93–1.62) and 1.40 (1.14–1.72), respectively, for BMI and alcohol consumption. Both metabolic signatures mediated the association between BMI and lifetime alcohol consumption and HCC with natural indirect effects, respectively, equal to 1.56 (1.24–1.96) and 1.09 (1.03–1.15), accounting for a proportion mediated of 100% and 24%. Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk. Impact: The understanding of the biological basis for the relationship between modifiable exposures and cancer would pave avenues for clinical and public health interventions on metabolic mediators. Cancer Epidemiol Biomarkers Prev; 27(5); 531–40. ©2018 AACR.

We examined whether specific input data and assumptions explain outcome differences in otherwise comparable health impact assessment models. Seven population health models estimating the impact of salt reduction on morbidity and mortality in western populations were compared on four sets of key features, their underlying assumptions and input data. Next, assumptions and input data were varied one by one in a default approach (the DYNAMO-HIA model) to examine how it influences the estimated health impact. Major differences in outcome were related to the size and shape of the dose-response relation between salt and blood pressure and blood pressure and disease. Modifying the effect sizes in the salt to health association resulted in the largest change in health impact estimates (33% lower), whereas other changes had less influence. Differences in health impact assessment model structure and input data may affect the health impact estimate. Therefore, clearly defined assumptions and transparent reporting for different models is crucial. However, the estimated impact of salt reduction was substantial in all of the models used, emphasizing the need for public health actions.

To test the effectiveness of a central venous catheter (CVC) insertion strategy and a hand hygiene (HH) improvement strategy to prevent central venous catheter-related bloodstream infections (CRBSI) in European intensive care units (ICUs), measuring both process and outcome indicators. Adult ICUs from 14 hospitals in 11 European countries participated in this stepped-wedge cluster randomised controlled multicentre intervention study. After a 6 month baseline, three hospitals were randomised to one of three interventions every quarter: (1) CVC insertion strategy (CVCi); (2) HH promotion strategy (HHi); and (3) both interventions combined (COMBi). Primary outcome was prospective CRBSI incidence density. Secondary outcomes were a CVC insertion score and HH compliance. Overall 25,348 patients with 35,831 CVCs were included. CRBSI incidence density decreased from 2.4/1000 CVC-days at baseline to 0.9/1000 (p

Background: In addition to blood pressure and cardiovascular disease, high-salt intake has been associated with renal diseases. The aim of this study is to estimate the potential health impact of salt reduction on chronic kidney disease (CKD) and end-stage kidney disease (ESKD) in the Netherlands.Methods: We developed a dynamic population health modeling tool to estimate the health impact of salt reduction on CKD and ESKD. We used data from the PREVEND study and extrapolated that to the Dutch population aged 30-75 years. We estimated the potential health impact of salt reduction comparing the current situation with the health impact of the adherence to the recommended maximum salt intake of 6 g/d.Results: In the recommended maximum intake scenario, a cumulative reduction in CKD of 1.1% (N = 290 000; interquartile range (IQR) = 249 000) and in ESKD of 3.2% (N = 470; IQR = 5080) would occur over a period of 20 years.Conclusions: Our health impact estimation showed that health benefits on CKD might be achieved when salt intake is reduced to the recommended maximum intake of 6 g/d.

Background Micro-simulation models of risk-factors and chronic diseases are built increasingly often, and each model starts with an initial population. Constructing such populations when no survey data covering all variables are available is no trivial task, often requiring complex methods based on several (untested) assumptions. In this paper, we propose a method for evaluating the merits of construction methods, and apply this to one specific method: the construction method used in the DYNAMO-HIA model. Methods The initial population constructed using the DYNAMO-HIA method is compared to another population constructed by starting a simulation with only newborns and simulating the course taken by one risk-factor and several diseases. In this simulation, the age- and sex-specific prevalence of the risk-factor is kept constant over time. Results Our simulations show that, in general, the DYNAMO-HIA method clearly outperforms a method that assumes independence of the risk-factor and the prevalence of diseases and independence between all diseases. In many situations the DYNAMO-HIA method performs reasonably well, but in some the proportion with the risk-factor for those with a disease is under- or overestimated by as much as 10 percentage points. For determining comorbidity between diseases linked by a common causal disease or a common risk-factor it also performs reasonably well. However, the current method performs poorly for determining the comorbidity between one disease caused by the other. Conclusion The DYNAMO-HIA methods perform reasonably well; they outperform a baseline assumption of independence between the risk-factor and diseases in the initial population. The method for determining the comorbidity between diseases that are causally linked needs improvement. Given the existing discrepancies for situations with high relative risks, however, developing more elaborate methods based on running simulation models to generate an initial population would be worthwhile.

ObjectiveTo compare the performance of the commonly used 24 h recall (24hR) with the more distinct duplicate portion (DP) as reference method for validation of fatty acid intake estimated with an FFQ.DesignIntakes of SFA, MUFA, n-3 fatty acids and linoleic acid (LA) were estimated by chemical analysis of two DP and by on average five 24hR and two FFQ. Plasma n-3 fatty acids and LA were used to objectively compare ranking of individuals based on DP and 24hR. Multivariate measurement error models were used to estimate validity coefficients and attenuation factors for the FFQ with the DP and 24hR as reference methods.SettingWageningen, the Netherlands.SubjectsNinety-two men and 106 women (aged 20–70 years).ResultsValidity coefficients for the fatty acid estimates by the FFQ tended to be lower when using the DP as reference method compared with the 24hR. Attenuation factors for the FFQ tended to be slightly higher based on the DP than those based on the 24hR as reference method. Furthermore, when using plasma fatty acids as reference, the DP showed comparable to slightly better ranking of participants according to their intake of n-3 fatty acids (0·33) and n-3:LA (0·34) than the 24hR (0·22 and 0·24, respectively).ConclusionsThe 24hR gives only slightly different results compared with the distinctive but less feasible DP, therefore use of the 24hR seems appropriate as the reference method for FFQ validation of fatty acid intake.

As FFQ are subject to measurement error, associations between self-reported intake by FFQ and outcome measures should be adjusted by correction factors obtained from a validation study. Whether the correction is adequate depends on the characteristics of the reference method used in the validation study. Preferably, reference methods should (1) be unbiased and (2) have uncorrelated errors with those in the FFQ. The aim of the present study was to assess the validity of the duplicate portion (DP) technique as a reference method and compare its validity with that of a commonly used reference method, the 24 h recall (24hR), for protein, K and Na using urinary markers as the unbiased reference method. For 198 subjects, two DP, two FFQ, two urinary biomarkers and between one and fifteen 24hR (web based and/or telephone based) were collected within 1·5 years. Multivariate measurement error models were used to estimate bias, error correlations between FFQ and DP or 24hR, and attenuation factors of these methods. The DP was less influenced by proportional scaling bias (0·58 for protein, 0·72 for K and 0·52 for Na), and correlated errors between DP and FFQ were lowest (protein 0·28, K 0·17 and Na 0·19) compared with the 24hR. Attenuation factors (protein 0·74, K 0·54 and Na 0·43) also indicated that the DP performed better than the 24hR. Therefore, the DP is probably the best available reference method for FFQ validation for nutrients that currently have no generally accepted recovery biomarker.

The aim of this study was to investigate (a) the mortality in a clinical cohort of patients with established rheumatoid arthritis in comparison with the general Dutch population over 15 years, (b) the trend in the mortality ratio during the study period, and (c) causes of death and compare these with the general population. In 1997, a sample of 1222 patients was randomly selected from the register of a large rheumatology outpatient clinic. Their mortality and primary causes of death between 1997 and 2012 were obtained from Statistics Netherlands. The standardized mortality ratio (SMR) for all-cause mortality and the number of life-years lost in the study period, adjusted for age, sex, and calendar year, were calculated. A linear poisson regression analysis was performed to evaluate change in all-cause SMR over time. Finally, the SMRs for cause-specific mortality were calculated. The mean age of the population at baseline was 60.4 (SD 15.4) years, and 72.6% of the patients were women. The estimated SMR (95% CI) for all-cause mortality was 1.54 (1.41, 1.67) with about one life-year lost over the study period. There was a trend to decreasing SMR (2% annually, p = .07). Mortality was higher compared with the general population for circulatory system diseases, respiratory system diseases, musculoskeletal system diseases, and digestive system diseases (p < .05). The observed mortality among patients with RA was 54% higher than in the general population after adjustment for age, sex and calendar year. More than one life-year was lost over 15 years, and the mortality tended to decrease over time. The mortality was higher for cardiovascular, respiratory, musculoskeletal and digestive diseases.

The added value of blood pressure (BP) trajectories for predicting cardiovascular disease (CVD) is currently unknown. We investigated the association of systolic BP (SBP) trajectories with CVD and all-cause mortality and compared these associations with those of average SBP, taking antihypertensive medication into account. Data from 762 participants of the Rancho Bernardo Study were used. SBP from five examinations (maximum) from 1984 to 2002 was used; mortality data were obtained from 2002 to 2013. SBP trajectories were derived using group-based trajectory modelling. Cox proportional hazards analysis was used to investigate associations of trajectories and average SBP with CVD and all-cause mortality, adjusted for age, sex, cholesterol, smoking, diabetes and antihypertensive medication. Mean baseline age was 65.7 years, and 67% were women. Four trajectories were identified, in which mean SBP increased by 5–12 mm Hg during 10 years. The highest trajectories were associated with two to three times greater CVD mortality and 1.5 times greater all-cause mortality risk, compared with the lowest trajectory. Each 20 mmHg increment in average SBP was associated with 1.4 times greater CVD mortality risk and 1.2 times all-cause mortality risk. Associations were not modified by antihypertensive medication (P-interaction>0.10). SBP trajectories were not superior to average SBP in predicting CVD and all-cause mortality. In the general middle-aged and older population of the Rancho Bernardo study, SBP trajectories provided no added value to average SBP in predicting CVD and all-cause mortality. Long-term average SBP levels and trajectories were significant predictors of CVD and all-cause mortality, irrespective of prescribed antihypertensive medication (which in the 1980s–1990s mainly were diuretics and β-blockers).Journal of Human Hypertension advance online publication, 23 March 2017; doi:10.1038/jhh.2017.20.

Background: In cohort studies, often only one baseline measurement of dietary intake is available. This may underestimate the strength of the association with cardiovascular diseases (CVD). Objective: The main objective is to compare the strength of the association of a Mediterranean style diet with CVD using one baseline measurement of diet versus three repeated measurements over a 10-year period. Design: We used dietary and lifestyle data of three rounds of the Doetinchem Cohort Study. At baseline, 7,769 persons aged 20-65 years were examined. Diet was assessed with a 178 item validated food-frequency questionnaire and operationalized with the Mediterranean Diet Score (MDS) ranging from 0 to 9. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CI). Analyses were adjusted for age, sex, and repeated measurements of smoking, sports, total energy intake, and educational level. Results: Comparing an MDS of ≥5.5-9 to an MDS of 0

A seasonal rise in tuberculosis (TB) notifications has been confirmed in several studies. Here, we examined one hypothesis for its cause: increased transmission of TB during wintertime due to crowding. Seasonality analysis was performed on actual and simulated notifications of clustered TB cases, which are considered to be representative of recent transmission, diagnosed from 1993 to 2004 in the Netherlands (n = 4,746). To test the hypothesis of winter crowding, notifications were simulated by adding patient delay and incubation period to an infection date randomly taken to be in winter in 80% of cases. The incubation periods were derived from frequency distributions for different TB disease localizations drawn from the literature. Seasonality analysis was performed using autocorrelation function plots and spectral analysis. Actual notifications showed strong seasonality in clustered TB and clustered extrapulmonary TB cases but not in clustered pulmonary TB cases. Analysis of simulated notifications revealed barely significant seasonality only in extrapulmonary TB cases. Our results suggest that increased transmission of TB during wintertime is unlikely to be the only cause of the seasonal peak in TB notifications. A factor closer to the notification date probably contributes to the seasonality observed in TB notifications.

ObjectiveTo describe long-term physical functioning and its association with somatic comorbidity and comorbid depression in patients with established rheumatoid arthritis (RA). MethodsLongitudinal data over a period of 11 years were collected from 882 patients with RA at study inclusion. Patient-reported outcomes were collected in 1997, 1998, 1999, 2002, and 2008. Physical functioning was measured with the Health Assessment Questionnaire and the physical component summary score of the Short Form 36 health survey. Somatic comorbidity was measured by a questionnaire including 12 chronic diseases. Comorbid depression was measured with the Center for Epidemiologic Studies Depression Scale. We distinguished 4 groups of patients based on comorbidity at baseline. ResultsSeventy-two percent of the patients at baseline were women. The mean +/- SD age was 59.3 +/- 14.8 years and the median disease duration was 5.0 years (interquartile range 2.0-14.0 years). For the total group of patients with RA, physical functioning improved over time. Patients with somatic comorbidity, comorbid depression, or both demonstrated worse physical functioning than patients without comorbidity at all data collection points. Both groups with comorbid depression had the lowest scores. Only patients with both somatic comorbidity and comorbid depression showed significantly less improvement in physical functioning over time. ConclusionBoth somatic comorbidity and comorbid depression were negatively associated with physical functioning during an 11-year followup period. Furthermore, their combination seems to be especially detrimental to physical functioning over time. These results emphasize the need to take somatic comorbidity and comorbid depression into account in the screening and treatment of patients with RA.

A common policy response to the rise in obesity prevalence is to undertake interventions in childhood, but it is an open question whether this is more effective than reducing the risk of becoming obese during adulthood. In this paper, we model the effect on health outcomes of (i) reducing the prevalence of obesity when entering adulthood; (ii) reducing the risk of becoming obese throughout adult life; and (iii) combinations of both approaches. We found that, while all approaches reduce the prevalence of chronic diseases and improve life expectancy, a given percentage reduction in obesity prevalence achieved during childhood had a smaller effect than the same percentage reduction in the risk of becoming obese applied throughout adulthood. A small increase in the probability of becoming obese during adulthood offsets a substantial reduction in prevalence of overweight/obesity achieved during childhood, with the gains from a 50% reduction in child obesity prevalence offset by a 10% increase in the probability of becoming obese in adulthood. We conclude that both policy approaches can improve the health profile throughout the life course of a cohort, but they are not equivalent, and a large reduction in child obesity prevalence may be reversed by a small increase in the risk of becoming overweight or obese in adulthood.

In this study, the relation between fruit and vegetable consumption and mortality was investigated within the European Prospective Investigation Into Cancer and Nutrition. Survival analyses were performed, including 451,151 participants from 10 European countries, recruited between 1992 and 2000 and followed until 2010. Hazard ratios, rate advancement periods, and preventable proportions to respectively compare risk of death between quartiles of consumption, to estimate the period by which the risk of death was postponed among high consumers, and to estimate proportions of deaths that could be prevented if all participants would shift their consumption 1 quartile upward. Consumption of fruits and vegetables was inversely associated with all-cause mortality (for the highest quartile, hazard ratio = 0.90, 95% confidence interval (CI): 0.86, 0.94), with a rate advancement period of 1.12 years (95% CI: 0.70, 1.54), and with a preventable proportion of 2.95%. This association was driven mainly by cardiovascular disease mortality (for the highest quartile, hazard ratio = 0.85, 95% CI: 0.77, 0.93). Stronger inverse associations were observed for participants with high alcohol consumption or high body mass index and suggested in smokers. Inverse associations were stronger for raw than for cooked vegetable consumption. These results support the evidence that fruit and vegetable consumption is associated with a lower risk of death.

AIM: Although some studies have examined the long-term effects of disasters, very little is known about severe persistent symptoms following disasters. The aim of the present study was to examine persistent mental health problems and to what extent disaster exposure predicts long-term persistent disturbances. METHODS: Following a major disaster, a four-wave study was conducted (surveys 2-3 weeks, 18 months, 4 years and 10 years after the event) that examined severe post-traumatic stress disorder (PTSD) symptomatology (Impact of Event Scale), anxiety and depression symptoms and sleeping problems (Symptom Check List-90-R), and use of physician-prescribed tranquilizers. Participants were affected adult Dutch native residents (n = 1083). At wave 2 and 3, a control group participated (n = 694). At wave 1, severity of disaster exposure was examined. Multiple imputation was used to target the problem of missing data across surveys due to non-response such as in the fourth wave (61%). RESULTS: In total, 6.7% (95% confidence interval [CI]: 5.1-8.2) developed persistent PTSD symptoms during the 10 years after the event. For anxiety, depression, sleeping problems these prevalences were 3.8% (95%CI: 2.7-5.0), 6.2% (95%CI: 4.7-7.6) and 4.8% (95%CI: 3.5-6.1) respectively. In total 1.3% (95%CI: 0.6-2.0) used tranquilizers at all waves. Approximately one out of 10 with severe symptoms 2-3 weeks after the event, developed persistent symptoms. Even in the long term, affected residents compared to controls had more often chronic anxiety symptoms and sleeping problems. High disaster exposure independently predicted persistent PTSD symptoms (adjusted odds ratio [adj. OR], 4.20; 95%CI: 2.02-8.74, P Language: en

Background: We aimed to assess absolute plasma-serum differences and differences in ranking of total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), and TC/HDLC ratio in children. Methods: We analysed data of 412 children participating in a Dutch birth cohort. TC, HDLC, and TC/HDLC ratio were determined in plasma at age 8 and 12 years and in serum at age 12 years. Results: Compared to serum, plasma TC at age 12 years was 0.07 mmol/l lower (95% CI -0.08 to -0.06), plasma HDLC was 0.06 mmol/l higher (95% CI 0.05-0.07), and plasma TC/HDLC ratio was 0.19 lower (95% CI -0.20 to -0.17) (p < 0.0001). Intraclass correlation coefficients (ICCs) for ranking of TC, HDLC, and TC/HDLC ratio at age 12 years were 0.970, 0.745, and 0.979, respectively. ICCs for ranking of 8- to 12-year change of TC, HDLC, and TC/HDLC ratio were 0.971, 0.957, and 0.955, respectively. Conclusions: Cholesterol was systematically different in plasma and serum, and use of plasma would result in a more favourable lipid profile of children (lower TC, higher HDLC, and lower TC/HDLC ratio). Nevertheless, consistency in ranking of children according to plasma or serum cholesterol concentrations was very high. Age-related change in cholesterol can be validly assessed by ranking the difference between serum concentrations at one age and plasma concentrations at another age.

Objective To estimate the impact of three daily salt consumption scenarios on the prevalence and incidence of ischaemic heart disease (IHD) and cerebrovascular disease in 2025 in the Turkish population aged ≥30 years using the DYNAMO Health Impact Assessment tool. Study design Statistical disease modelling study. Methods DYNAMO health impact assessment was populated using data from Turkey to estimate the prevalence and incidence of IHD and cerebrovascular disease in 2025. TurkSTAT data were used for demographic data, and national surveys were used for salt consumption and disease-specific burden. Three salt consumption scenarios were modelled: (1) reference scenario: mean salt consumption stays the same from 2012–2013 until 2025; (2) gradual decline: daily salt intake reduces steadily by 0.47 g per year by lowering salt intake from bread by 50% and from table salt by 40% by 2025; and (3) World Health Organization (WHO) advice: daily salt intake of 5 g per day from 2013 until 2025. Results The gradual decline scenario would lead to a decrease in the prevalence of IHD and cerebrovascular disease by 0.3% and 0.2%, respectively, and a decrease in the incidence by 0.6 and 0.4 per 1000, respectively. Following WHO's advice would lead to a decrease in the prevalence of IHD and cerebrovascular disease by 0.8% and 0.5%, respectively, and a decrease in the incidence by 1.0 and 0.7 per 1000, respectively. Conclusion This model indicates that Turkey can lower its future cardiovascular disease burden by following the gradual decline scenario. Following WHO's advice would achieve an even greater benefit.