Estimating the contribution of overweight and obesity to ethnic inequalities in cardio-metabolic diseases in the Netherlands: a simulation study.

OBJECTIVES: Overweight and obesity (OWOB) starts in childhood, influences adult cardiovascular risk, and is not equally distributed across ethnic groups. It is unclear which effects can be expected from reductions in OWOB across the life course on inequalities in cardio-metabolic diseases in a multi-ethnic population. This study aims to estimate the effects of three scenarios of changes in OWOB (the Normal-Weight-for-All scenario, the No-Ethnic-Difference-over-the-Life-Course scenario, the and No-Ethnic-Differences-in-Childhood scenario). STUDY DESIGN: A simulation study. METHODS: We combine data from multiple data sources and use the Dynamic Modeling for Health Impact Assessment (DYNAMO-HIA) model to estimate the effects of three scenarios on the cumulative incidence of diabetes mellitus, ischaemic heart disease (IHD) and stroke between 18 and 70 years in the five largest ethnic groups in the Netherlands. RESULTS: In the scenario where all individuals have normal weight, the cumulative incidence decreased in all ethnic minority groups for all diseases, with largest decreases among South-Asian Surinamese, where the reduction of diabetes incidence exceeded 50%. In the scenario where the prevalence of OWOB in each ethnic-minority group was reduced to the current level among the Dutch-origin population, ethnic inequalities in cardio-metabolic diseases were substantially reduced, particularly when lowered prevalence of OWOB persisted across the lifespan. Reductions were the largest for diabetes and for the Asian Surinamese population. CONCLUSIONS: A substantial part of the well-known ethnic inequalities in incidence of diabetes, IHD, and stroke can be attributed to OWOB. Interventions aimed at reducing OWOB have clear potential to reduce the health inequalities in these outcomes, especially for diabetes, in particular when they have an impact across the lifespan.

Using random forest to identify longitudinal predictors of health in a 30-year cohort study.

Due to the wealth of exposome data from longitudinal cohort studies that is currently available, the need for methods to adequately analyze these data is growing. We propose an approach in which machine learning is used to identify longitudinal exposome-related predictors of health, and illustrate its potential through an application. Our application involves studying the relation between exposome and self-perceived health based on the 30-year running Doetinchem Cohort Study. Random Forest (RF) was used to identify the strongest predictors due to its favorable prediction performance in prior research. The relation between predictors and outcome was visualized with partial dependence and accumulated local effects plots. To facilitate interpretation, exposures were summarized by expressing them as the average exposure and average trend over time. The RF model's ability to discriminate poor from good self-perceived health was acceptable (Area-Under-the-Curve = 0.707). Nine exposures from different exposome-related domains were largely responsible for the model's performance, while 87 exposures seemed to contribute little to the performance. Our approach demonstrates that ML can be interpreted more than widely believed, and can be applied to identify important longitudinal predictors of health over the life course in studies with repeated measures of exposure. The approach is context-independent and broadly applicable.

Association between season of vaccination and antibody levels against infectious diseases.

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 children vs. 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 a P-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.

Time lag between immigration and tuberculosis rates in immigrants in the Netherlands: a time-series analysis.

SETTING AND OBJECTIVE: In low-incidence countries, most tuberculosis (TB) cases are foreign-born. We explored the temporal relationship between immigration and TB in first-generation immigrants between 1995 and 2012 to assess whether immigration can be a predictor for TB in immigrants from high-incidence countries. DESIGN: We obtained monthly data on immigrant TB cases and immigration for the three countries of origin most frequently represented among TB cases in the Netherlands: Morocco, Somalia and Turkey. The best-fit seasonal autoregressive integrated moving average (SARIMA) model to the immigration time-series was used to prewhiten the TB time series. The cross-correlation function (CCF) was then computed on the residual time series to detect time lags between immigration and TB rates. RESULTS: We identified a 17-month lag between Somali immigration and Somali immigrant TB cases, but no time lag for immigrants from Morocco and Turkey. CONCLUSION: The absence of a lag in the Moroccan and Turkish population may be attributed to the relatively low TB prevalence in the countries of origin and an increased likelihood of reactivation TB in an ageing immigrant population. Understanding the time lag between Somali immigration and TB disease would benefit from a closer epidemiological analysis of cohorts of Somali cases diagnosed within the first years after entry.

Blood pressure trajectories in relation to cardiovascular mortality: The Rancho Bernardo Study.

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 ß-blockers).

Mortality in patients with rheumatoid arthritis: a 15-year prospective cohort study.

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.

Predicting the health impact of lowering salt consumption in Turkey using the DYNAMO health impact assessment tool.

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.

Health care costs attributable to overweight calculated in a standardized way for three European countries.

This article presents a tool to calculate health care costs attributable to overweight in a comparable and standardized way. The purpose is to describe the methodological principles of the tool and to put it into use by calculating and comparing the costs attributable to overweight for The Netherlands, Germany and Czech Republic. The tool uses a top-down and prevalence-based approach, consisting of five steps. Step one identifies overweight-related diseases and age- and gender-specific relative risks. Included diseases are ischemic heart disease, stroke, hypertension, type 2 diabetes mellitus, colorectal cancer, postmenopausal breast cancer, endometrial cancer, kidney cancer and osteoarthritis. Step two consists of collecting data on the age- and gender-specific prevalence of these diseases. Step three uses the population-attributable prevalence to determine the part of the prevalence of these diseases that is attributable to overweight. Step four calculates the health care costs associated with these diseases. Step five calculates the costs of these diseases that are attributable to overweight. Overweight is responsible for 20-26% of the direct costs of included diseases, with sensitivity analyses varying this percentage between 15-31%. Percentage of costs attributable to obesity and preobesity is about the same. Diseases with the highest percentage of costs due to overweight are diabetes, endometrial cancer and osteoarthritis. Disease costs attributable to overweight as a percentage of total health care expenditures range from 2 to 4%. Data are consistent for all three countries, resulting in roughly a quarter of costs of included diseases being attributable to overweight.

Association of Somatic Comorbidities and Comorbid Depression With Mortality in Patients With Rheumatoid Arthritis: A 14-Year Prospective Cohort Study.

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.

Screen time, adiposity and cardiometabolic markers: mediation by physical activity, not snacking, among 11-year-old children.

BACKGROUND: There is evidence for a relation of TV viewing with adiposity and increased cardiometabolic risk factors in children and adolescents. It is unclear to what extent this relation is mediated by snacking and lack of physical activity. We determined whether associations of screen time with adiposity and cardiometabolic markers were mediated by these behaviours. METHODS: Children from a population-representative Dutch birth cohort (n=1447) reported screen time and other lifestyle factors by a questionnaire around the age of 11 years (range 10-14) and had anthropometry and cardiometabolic markers measured around the age of 12 years (range 12-14). Adjusted associations of screen time with snacking, physical activity, adiposity and cardiometabolic markers (total-to-high-density lipoprotein cholesterol (TC/HDLC) ratio, blood pressure, glycated haemoglobin) were assessed by using formal mediation analysis. We tested the hypothesized paths by structural equation modeling, which allows quantification of the indirect effects associated with potential mediators. RESULTS: Children with ⩾20 h screen time per week consumed more snacks (1.9 vs 1.3 portions per day) and were less physically active (4.3 vs 4.8 days per week) than children with maximum 6 h screen time. Screen time was directly associated with higher adiposity (standardized ß=0.10-0.12 depending on the outcome, P<0.001), and indirectly through less physical activity. The association of screen time with TC/HDLC ratio was almost completely mediated by adiposity (ß=0.39, P<0.0001), and to a minor extent by physical activity (ß=-0.06, P=0.02). There was no direct association of screen time with TC/HDLC ratio. CONCLUSIONS: The adverse association of screen time with adiposity was partly mediated by physical activity, but not by snacking. The association of screen time with TC/HDLC ratio was almost completely mediated by adiposity. Our results may suggest that future efforts in society and public health should be directed to replace screen time with physical activity for reducing children's adiposity and cardiometabolic risk.

Relationship of coagulation and fibrinolytic variables with arterial structure and function in Africans.

INTRODUCTION: Although both coagulation and fibrinolysis are associated with cardiovascular disease (CVD) the underlying nature and pathways of many of these associations are still unclear. Our aim was to determine which of the current or 5-year prior levels of total fibrinogen, fibrinogen γ', plasminogen activator inhibitor-1 (PAI-1act) and global fibrinolytic potential were the stronger determinant of arterial structure and function. MATERIALS AND METHODS: This prospective study consisted of 2010 Africans over the age of 35 years with 5-year follow-up data available for 1288 participants. Cardiovascular measurements included arterial stiffness, blood pressure and carotid intima media thickness. RESULTS: Fibrinogen γ' showed stronger associations with blood pressure than total fibrinogen also in the presence of other CVD risk factors. PAI-1act was positively associated with blood pressure both cross-sectionally and prospectively, with the longitudinal association being the stronger determinant, also after adjustment for known CVD risk factors. Clot lysis time (CLT) was positively associated, both prospectively and cross-sectionally, with intima media thickness and negatively with markers of arterial stiffness but not after adjustment for known CVD risk factors. CONCLUSIONS: Fibrinogen γ' was more strongly associated with CVD function than total fibrinogen. PAI-1act was significantly associated with blood pressure with changes in PAI-1 levels preceding changes in blood pressure. Different mechanisms may be at play determining arterial wall stiffness/thickening and blood pressure as observed from the opposing associations with PAI-1act and CLT. CLT was not independently related to cardiovascular measures as its associations were weakened in the presence of other known CVD risk factors.

Similar seasonal peak in clustered and unique extra-pulmonary tuberculosis notifications: winter crowding hypothesis ruled out?

BACKGROUND: The incidence of extra-pulmonary tuberculosis (EPTB) in the Netherlands shows a seasonal trend, with a peak in spring and a trough in autumn. Possible causes of this peak are winter crowding and a seasonal decrease in immune competence in spring. A third explanation may be a reporting bias. OBJECTIVE: To investigate the role of winter crowding by a time-series analysis of notification data. DNA fingerprinting clustering status can differentiate between recent and remote infections. Seasonality in clustered cases would reflect enhanced transmission in winter and/or seasonally lowered immunity, while seasonality in unique cases would only reflect seasonally lowered immunity. METHODS: We fitted (seasonal) auto-regressive moving average models to culture-positive TB notifications in the Netherlands (1993-2008) to assess seasonality. We then used seasonal trend Loess decompositions to derive the seasonal pattern, and compared the heights of the seasonal peaks. RESULTS: Clustered and unique EPTB notifications showed a seasonal trend that was absent in clustered and unique PTB notifications. The seasonal peak in clustered EPTB cases was not significantly higher than in unique EPTB cases. CONCLUSIONS: The similar timing and height of the seasonal peak of clustered and unique EPTB cases suggests that winter crowding is unlikely to cause the seasonal trend in notifications.

Modelling obesity outcomes: reducing obesity risk in adulthood may have greater impact than reducing obesity prevalence in childhood.

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.

Long-term physical functioning and its association with somatic comorbidity and comorbid depression in patients with established rheumatoid arthritis: a longitudinal study.

OBJECTIVE: To describe long-term physical functioning and its association with somatic comorbidity and comorbid depression in patients with established rheumatoid arthritis (RA). METHODS: Longitudinal 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. RESULTS: Seventy-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. CONCLUSION: Both 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.

Smoking and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported. METHODS: During 1992 and 2000, lifestyle information was assessed via questionnaires and personal interview in a cohort of 145,112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer. RESULTS: Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR=0.90, 95% CI: 0.83-0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR=1.81, 95% CI: 1.11-2.93; RR=1.38, 95% CI: 1.01-1.87, respectively). CONCLUSION: The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies.

Handover training: does one size fit all? The merits of mass customisation.

BACKGROUND: Experts have recommended training and standardisation as promising approaches to improve handovers and minimise the negative consequences of discontinuity of care. Yet the content and delivery of handover training have been only superficially examined and described in literature. OBJECTIVE: The aim of this study was to formulate recommendations for effective handover training and to examine whether standardisation is a viable approach to training large numbers of healthcare professionals. METHODS: A training needs analysis was conducted by means of a questionnaire, which was filled out by 96 healthcare professionals in primary and secondary care in the Netherlands, Spain, Sweden and Poland. Preferences and recommendations regarding training delivery aspects and training topics that should be included in the handover training were measured. RESULTS: The majority of the participants recommended a short conventional training session with practice assignments, to be completed in small, multidisciplinary groups. Formal examination, e-learning and self-study were not favoured. Recommended training topics were: communication skills, standardised procedures, knowing what to hand over, alertness to vulnerable patient groups and awareness of responsibility. CONCLUSIONS: The idea of completely standardised handover training is not in line with the identified differences in preferences and recommendations between different handover stakeholders. Mass customisation of training, in which generic training is adapted to local or individual needs, presents a promising solution to address general and specific needs, while containing the financial and time costs of designing and delivering handover training.

Variety in vegetable and fruit consumption and the risk of gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition.

Diets high in vegetables and fruits have been suggested to be inversely associated with risk of gastric cancer. However, the evidence of the effect of variety of consumption is limited. We therefore investigated whether consumption of a variety of vegetables and fruit is associated with gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition study. Data on food consumption and follow-up on cancer incidence were available for 452,269 participants from 10 European countries. After a mean follow-up of 8.4 years, 475 cases of gastric and esophageal adenocarcinomas (180 noncardia, 185 cardia, gastric esophageal junction and esophagus, 110 not specified) and 98 esophageal squamous cell carcinomas were observed. Diet Diversity Scores were used to quantify the variety in vegetable and fruit consumption. We used multivariable Cox proportional hazard models to calculate risk ratios. Independent from quantity of consumption, variety in the consumption of vegetables and fruit combined and of fruit consumption alone were statistically significantly inversely associated with the risk of esophageal squamous cell carcinoma (continuous hazard ratio per 2 products increment 0.88; 95% CI 0.79-0.97 and 0.76; 95% CI 0.62-0.94, respectively) with the latter particularly seen in ever smokers. Variety in vegetable and/or fruit consumption was not associated with risk of gastric and esophageal adenocarcinomas. Independent from quantity of consumption, more variety in vegetable and fruit consumption combined and in fruit consumption alone may decrease the risk of esophageal squamous cell carcinoma. However, residual confounding by lifestyle factors cannot be excluded.

Estimating net transition probabilities from cross-sectional data with application to risk factors in chronic disease modeling.

A problem occurring in chronic disease modeling is the estimation of transition probabilities of moving from one state of a categorical risk factor to another. Transitions could be obtained from a cohort study, but often such data may not be available. However, under the assumption that transitions remain stable over time, age specific cross-sectional prevalence data could be used instead. Problems that then arise are parameter identifiability and the fact that age dependent cross-sectional data are often noisy or are given in age intervals. In this paper we propose a method to estimate so-called net annual transition probabilities from cross-sectional data, including their uncertainties. Net transitions only describe the net inflow or outflow into a certain risk factor state at a certain age. Our approach consists of two steps: first, smooth the data using multinomial P-splines, second, from these data estimate net transition probabilities. This second step can be formulated as a transportation problem, which is solved using the simplex algorithm from linear programming theory. A sensible specification of the cost matrix is crucial to get meaningful results. Uncertainties are assessed by parametric bootstrapping. We illustrate our method using data on body mass index. We conclude that this method provides a flexible way of estimating net transitions and that the use of net transitions has implications for model dynamics, for example when modeling interventions.

The influence of population characteristics on variation in general practice based morbidity estimations.

BACKGROUND: General practice based registration networks (GPRNs) provide information on morbidity rates in the population. Morbidity rate estimates from different GPRNs, however, reveal considerable, unexplained differences. We studied the range and variation in morbidity estimates, as well as the extent to which the differences in morbidity rates between general practices and networks change if socio-demographic characteristics of the listed patient populations are taken into account. METHODS: The variation in incidence and prevalence rates of thirteen diseases among six Dutch GPRNs and the influence of age, gender, socio economic status (SES), urbanization level, and ethnicity are analyzed using multilevel logistic regression analysis. Results are expressed in median odds ratios (MOR). RESULTS: We observed large differences in morbidity rate estimates both on the level of general practices as on the level of networks. The differences in SES, urbanization level and ethnicity distribution among the networks' practice populations are substantial. The variation in morbidity rate estimates among networks did not decrease after adjusting for these socio-demographic characteristics. CONCLUSION: Socio-demographic characteristics of populations do not explain the differences in morbidity estimations among GPRNs.

Fruits and vegetables consumption and the risk of histological subtypes of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

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.