Motives for withdrawal of participation in biobanking and participants' willingness to allow linkages of their data.

Data repositories, like research biobanks, seek to optimise the number of responding participants while simultaneously attempting to increase the amount of data donated per participant. Such efforts aim to increase the repository's value for its uses in medical research to contribute to improve health care, especially when data linkage is permitted by participants. We investigated individuals' motives for participating in such projects and potential reasons for their withdrawal from participation in a population-based biobank. In addition, we analysed how these motives were related to various characteristics of the participants and their willingness to permit data linkage to their personal data for research. These questions were explored using a sample of participants in the Dutch Lifelines biobank (n = 2615). Our results indicated that motives for participation and withdrawal were premised on benefits or harm to society and to the individuals themselves. Although general values and trust both played key roles in participation, potential withdrawal and willingness to permit data linkage, they were differentially associated with motives for participation and withdrawal. These findings support and nuance previous findings by highlighting the distinctiveness and complexity of decision making regarding participation in or withdrawal from data donation. We suggest some new directions for improving recruitment, retention and safeguarding strategies in biobanking. In addition, our data provide initial evidence regarding how factors may relate with the probability that individuals will agree to data linkages, when controlling for their unique effects. Future research should further investigate how perceptions of harm and benefits may influence decision making on withdrawal of participation.

Effect of metabolic genetic variants on long-term disease comorbidity in patients with type 2 diabetes.

Underlying genetic determinants contribute to developing type 2 diabetes (T2D) future diseases. The present study aimed to identify which genetic variants are associated with the incident of the major T2D co-morbid disease. First, we conducted a discovery study by investigating the genetic associations of comorbid diseases within the framework of the Utrecht Cardiovascular Pharmacogenetic studies by turning information of > 25 years follow-up data of 1237 subjects whom were genotyped and included in the discovery study. We performed Cox proportional-hazards regression to examine associations between genetic variants and comorbid diseases including cardiovascular diseases (CVD), chronic eye disease, cancer, neurologic diseases and chronic kidney disease. Secondly, we replicated our findings in two independent cohorts consisting of 1041 subjects. Finally, we performed a meta-analysis by combining the discovery and two replication cohorts. We ascertained 390 (39.7%) incident cases of CVD, 182 (16.2%) of chronic eye disease, 155 (13.8%) of cancer, 31 (2.7%) of neurologic disease and 13 (1.1%) of chronic kidney disease during a median follow-up of 10.2 years. In the discovery study, we identified a total of 39 Single Nucleotide Polymorphisms (SNPs) associated with comorbid diseases. The replication study, confirmed that rs1870849 and rs8051326 may play a role in the incidence of chronic eye disease in T2D patients. Half of patients developed at least one comorbid disease, with CVD occurring most often and earliest followed by chronic eye disease. Further research is needed to confirm the associations of two associated SNPs with chronic eye disease in T2D.

Demographic and prosocial intrapersonal characteristics of biobank participants and refusers: the findings of a survey in the Netherlands.

Research in genetics relies heavily on voluntary contributions of personal data. We aimed to acquire insights into the differences between participants and refusers of participation in a Dutch population-based biobank. Accordingly, we assessed the demographic and prosocial intrapersonal characteristics of respondents who participated (n = 2615) or refused to participate (n = 404) in the Lifelines biobank and databank. Our results indicated that health-related values critically influence participation decisions. The participation threshold for Lifelines was determined by an absence of health-related values and of trust in government. Therefore, considering these factors in communication and recruitment strategies could enhance participation in biomedical research. No indications were found of a stronger general prosociality of participants or their trust in researchers beyond the context of biobanking. This emphasizes the contextual understanding of the decision of participation in biobanking. Our findings may contribute to improving recruitment strategies by incorporating relevant values and/or highlighting prosocial benefits. Moreover, they foreground the need to address trust issues in collaborations between data repositories and commercial companies. Future research should explore how prosocial intrapersonal characteristics drive participation and withdrawal decisions and relate to contextual attributes.

Infant Motor Milestones and Childhood Overweight: Trends over Two Decades in A Large Twin Cohort.

BACKGROUND: Poor motor skill competence may influence energy balance with childhood overweight as a result. Our aim was to investigate whether the age of motor milestone achievement has changed over the past decades and whether this change may contribute to the increasing trend observed in childhood overweight. METHODS: Motor skill competence was assessed in children from the Young Netherlands Twin Register born between 1987 and 2007. Follow-up ranged from 4 up to 10 years. Weight and height were assessed at birth, 6 months, 14 months, and 2, 4, 7, and 10 years. RESULTS: Babies born in later cohorts achieved their motor milestones 'crawling', 'standing', and 'walking unassisted' later compared to babies born in earlier cohorts (N = 18,514, p < 0.001). The prevalence of overweight at age 10 was higher in later cohorts (p = 0.033). The increase in overweight at age 10 was not explained by achieving motor milestones at a later age and this persisted after adjusting for gestational age, sex, and socioeconomic status. CONCLUSION: Comparing children born in 1987 to those born in 2007, we conclude that children nowadays achieve their motor milestones at a later age. This does not however, explain the increasing trend in childhood overweight.

Trust in Centralized Large-Scale Data Repository: A Qualitative Analysis.

Exponential increases in digital data and calls for participation in human research raise questions about when and why individuals voluntarily provide personal data. We conducted 36 in-depth interviews with ex-participants, participants, and nonparticipants in a biobank to identify key factors influencing trust in centralized large-scale data repository for human research. Our findings indicated that trust depends strongly on whether such data repository benefits the public, the interests of data collectors, the characteristics of the collected data, and application of informed consent for retaining control over personal data. Concerns about the aims and range of data repository appeared to influence withdrawal of participation. Our findings underscore ethical and practical issues relating to data collection and consent procedures in human research.

Later achievement of infant motor milestones is related to lower levels of physical activity during childhood: the GECKO Drenthe cohort.

BACKGROUND: The aim of this study is to investigate whether age of infant motor milestone achievement is related to levels of physical activity (PA), weight status and blood pressure at age 4-7 years of age. METHODS: In the Dutch GECKO (Groningen Expert Center of Kids with Obesity) Drenthe cohort, the age of achieving the motor milestone 'walking without support' was reported by parents. Weight status and blood pressure were assessed by trained health nurses and PA was measured using the Actigraph GT3X between age 4 and 7 years. RESULTS: Adjusted for children's age, sex and the mother's education level, infants who achieved walking without support at a later age, spent more time in sedentary behaviour during childhood and less time in moderate-to-vigorous PA. Later motor milestones achievement was not related to higher BMI Z-score, waist circumference Z-score, diastolic or systolic blood pressure. CONCLUSION: The results of this study indicate that a later age of achieving motor milestone within the normal range have a weak relation to lower PA levels at later age. It is not likely that this will have consequences for weight status or blood pressure at 4-7 years of age.

What If Pregnancy Is Not Seventh Heaven? The Influence of Specific Life Events during Pregnancy and Delivery on the Transition of Antenatal into Postpartum Anxiety and Depression.

INTRODUCTION: Postpartum symptoms of anxiety and depression are known to have a negative impact on mother and child, and major life events constitute a major risk factor for these symptoms. We aimed to investigate to what extent specific life events during pregnancy, delivery complications, unfavorable obstetric outcomes, and antenatal levels of anxiety or depression symptoms were independently associated with postpartum levels of anxiety and depression symptoms. METHODS: Within a prospective population-based cohort study (n = 3842) in The Netherlands, antenatal symptoms of anxiety or depression were measured at the end of the first trimester and at five months postpartum. Antenatal life events were assessed during the third trimester, and information on delivery and obstetric outcomes was obtained from midwives and gynecologists. Linear regression analyses were performed to quantify the associations. RESULTS: Antenatal levels of both anxiety and depression symptoms were associated with postpartum levels of anxiety and depression symptoms. Life events related to health and sickness of self or loved ones, to the relation with the partner or conflicts with loved ones, or to work, finance, or housing problems were significantly associated with higher postpartum levels of anxiety symptoms (p < 0.001) and depression symptoms (p < 0.001) adjusted for antenatal levels. No statistically significant results were observed for pregnancy-related events, delivery complications, or unfavorable obstetric outcomes. CONCLUSIONS: Women with increased antenatal levels of anxiety or depression symptoms are at increased risk of elevated levels of both postpartum depression and anxiety symptoms. Experiencing life events during pregnancy that were not related to the pregnancy was associated with higher levels of anxiety and depression in the postpartum period, as opposed to pregnancy-related events, delivery complications, or unfavorable obstetric outcomes. These results suggest that events during pregnancy but not related to the pregnancy and birth are a highly important predictor for postpartum mental health.

WITHDRAWN: Interventions for treating obesity in children.

BACKGROUND: Child and adolescent obesity is increasingly prevalent, and can be associated with significant short- and long-term health consequences. OBJECTIVES: To assess the efficacy of lifestyle, drug and surgical interventions for treating obesity in childhood. SEARCH METHODS: We searched CENTRAL on The Cochrane Library Issue 2 2008, MEDLINE, EMBASE, CINAHL, PsycINFO, ISI Web of Science, DARE and NHS EED. Searches were undertaken from 1985 to May 2008. References were checked. No language restrictions were applied. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) of lifestyle (i.e. dietary, physical activity and/or behavioural therapy), drug and surgical interventions for treating obesity in children (mean age under 18 years) with or without the support of family members, with a minimum of six months follow up (three months for actual drug therapy). Interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data following the Cochrane Handbook. Where necessary authors were contacted for additional information. MAIN RESULTS: We included 64 RCTs (5230 participants). Lifestyle interventions focused on physical activity and sedentary behaviour in 12 studies, diet in 6 studies, and 36 concentrated on behaviorally orientated treatment programs. Three types of drug interventions (metformin, orlistat and sibutramine) were found in 10 studies. No surgical intervention was eligible for inclusion. The studies included varied greatly in intervention design, outcome measurements and methodological quality.Meta-analyses indicated a reduction in overweight at 6 and 12 months follow up in: i) lifestyle interventions involving children; and ii) lifestyle interventions in adolescents with or without the addition of orlistat or sibutramine. A range of adverse effects was noted in drug RCTs. AUTHORS' CONCLUSIONS: While there is limited quality data to recommend one treatment program to be favoured over another, this review shows that combined behavioural lifestyle interventions compared to standard care or self-help can produce a significant and clinically meaningful reduction in overweight in children and adolescents. In obese adolescents, consideration should be given to the use of either orlistat or sibutramine, as an adjunct to lifestyle interventions, although this approach needs to be carefully weighed up against the potential for adverse effects. Furthermore, high quality research that considers psychosocial determinants for behaviour change, strategies to improve clinician-family interaction, and cost-effective programs for primary and community care is required.

Long-term Air Pollution Exposure, Genome-wide DNA Methylation and Lung Function in the LifeLines Cohort Study.

BACKGROUND: Long-term air pollution exposure is negatively associated with lung function, yet the mechanisms underlying this association are not fully clear. Differential DNA methylation may explain this association. OBJECTIVES: Our main aim was to study the association between long-term air pollution exposure and DNA methylation. METHODS: We performed a genome-wide methylation study using robust linear regression models in 1,017 subjects from the LifeLines cohort study to analyze the association between exposure to nitrogen dioxide (NO2) and particulate matter (PM2.5, fine particulate matter with aerodynamic diameter ≤2.5 µm; PM10, particulate matter with aerodynamic diameter ≤10 µm) and PM2.5absorbance, indicator of elemental carbon content (estimated with land-use-regression models) with DNA methylation in whole blood (Illumina® HumanMethylation450K BeadChip). Replication of the top hits was attempted in two independent samples from the population-based Cooperative Health Research in the Region of Augsburg studies (KORA). RESULTS: Depending on the p-value threshold used, we found significant associations between NO2 exposure and DNA methylation for seven CpG sites (Bonferroni corrected threshold p<1.19×10-7) or for 4,980 CpG sites (False Discovery Rate<0.05). The top associated CpG site was annotated to the PSMB9 gene (i.e., cg04908668). None of the seven Bonferroni significant CpG-sites were significantly replicated in the two KORA-cohorts. No associations were found for PM exposure. CONCLUSIONS: Long-term NO2 exposure was genome-wide significantly associated with DNA methylation in the identification cohort but not in the replication cohort. Future studies are needed to further elucidate the potential mechanisms underlying NO2-exposure-related respiratory disease. https://doi.org/10.1289/EHP2045.

Combining informal care and paid work: The use of work arrangements by working adult-child caregivers in the Netherlands.

An increasing number of people combine paid work with the provision of informal care for a loved one. This combination of work and care may cause difficulties, necessitating adaptations at work, i.e. work arrangements. The present study explores what types of work arrangements are used by working caregivers, and which caregiver, care and work characteristics are associated with the use of these work arrangements. Within the Lifelines Informal Care Add-on Study (Lifelines ICAS), data on 965 Dutch informal caregivers in the North of the Netherlands were collected between May 2013 and July 2014 (response rate 48%), and data on 333 working adult-child caregivers (aged 26-68 years, 82% female) were used in this study. A small majority (56%) of the working caregivers used one or more work arrangement(s): taking time off (41%), individual agreements with supervisor (30%), formal care leave arrangement (13%), and reduction in paid work hours (6%). Logistic regression analyses showed that long working hours (OR 1.06, 95% CI 1.01-1.08), and the experience of more health problems (OR 2.54, 95% CI 1.56-4.05) or a disrupted schedule due to caregiving (OR 2.50, 95% CI 1.66-3.78) increased the chance to have used one or more work arrangements. Lower educated working caregivers were less likely to have used a formal care leave arrangement (tertiary vs. primary education OR 2.75, 95% CI 1.13-6.67; tertiary vs. secondary education OR 1.27, 95% CI 1.27-5.09). Policy makers should inform working caregivers about the availability of the different work arrangements, with specific attention for low educated working caregivers. Employers need to consider a more caregiver-friendly policy, as almost half of the working adult-child caregivers did not use any work arrangement.

Changing the obesogenic environment to improve cardiometabolic health in residential patients with a severe mental illness: cluster randomised controlled trial.

BackgroundFor patients with severe mental illness (SMI) in residential facilities, adopting a healthy lifestyle is hampered by the obesity promoting (obesogenic) environment.AimsTo determine the effectiveness of a 12-month lifestyle intervention addressing the obesogenic environment with respect to diet and physical activity to improve waist circumference and cardiometabolic risk factors v. care as usual (Dutch Trial Registry: NTR2720).MethodIn a multisite cluster randomised controlled pragmatic trial, 29 care teams were randomised into 15 intervention (365 patients) and 14 control teams (371 patients). Intervention staff were trained to improve the obesogenic environment.ResultsWaist circumference decreased 1.51 cm (95% CI -2.99 to -0.04) in the intervention v. control group after 3 months and metabolic syndrome z-score decreased 0.22 s.d. (95% CI -0.38 to -0.06). After 12 months, the decrease in waist circumference was no longer statistically significantly different (-1.28 cm, 95% CI -2.79 to 0.23, P=0.097).ConclusionsTargeting the obesogenic environment of residential patients with SMI has the potential to facilitate reduction of abdominal adiposity and cardiometabolic risk, but maintaining initial reductions over the longer term remains challenging.

Residential Air Pollution and Associations with Wheeze and Shortness of Breath in Adults: A Combined Analysis of Cross-Sectional Data from Two Large European Cohorts.

BACKGROUND: Research examining associations between air pollution exposure and respiratory symptoms in adults has generally been inconclusive. This may be related in part to sample size issues, which also preclude analysis in potentially vulnerable subgroups. OBJECTIVES: We estimated associations between air pollution exposures and the prevalence of wheeze and shortness of breath using harmonized baseline data from two very large European cohorts, Lifelines (2006-2013) and UK Biobank (2006-2010). Our aim was also to determine whether the relationship between air pollution and respiratory symptom prevalence differed between individuals with different characteristics. METHODS: Cross-sectional analyses explored associations between prevalence of self-reported wheeze and shortness of breath and annual mean particulate matter with aerodynamic diameter <2.5µm, 2.5-10µm, and <10µm (PM2.5, PMcoarse, and PM10, respectively) and nitrogen dioxide (NO2) concentrations at place of residence using logistic regression. Subgroup analyses and tests for interaction were performed for age, sex, smoking status, household income, obesity status, and asthma status. RESULTS: All PM exposures were associated with respiratory symptoms based on single-pollutant models, with the largest associations seen for PM2.5 with prevalence of wheezing {odds ratio (OR)=1.16 per 5µg/m³ [95% confidence interval (CI): 1.11, 1.21]} and shortness of breath [OR=1.61 per 5µg/m³ (95% CI: 1.45, 1.78)]. The association between shortness of breath and a 5-µg/m³ increment in PM2.5 was significantly higher for individuals from lower-[OR=1.73 (95% CI: 1.52, 1.97)] versus higher-income households [OR=1.31 (95% CI: 1.11, 1.55); p-interaction=0.005), whereas the association between PM2.5 and wheeze was limited to lower-income participants [OR=1.30 (95% CI: 1.22, 1.38) vs. OR=1.02; (95% CI: 0.96, 1.08); p-interaction<0.001]. Exposure to NO2 also showed positive associations with wheeze and shortness of breath. CONCLUSION: Exposure to PM and NO2 air pollution was associated with the prevalence of wheeze and shortness of breath in this large study, with stronger associations between PM2.5 and both outcomes among lower- versus higher-income participants. https://doi.org/10.1289/EHP1353.

The impact of older person's frailty on the care-related quality of life of their informal caregiver over time: results from the TOPICS-MDS project.

PURPOSE: To examine the impact of changes in an older person's frailty on the care-related quality of life of their informal caregiver. METHODS: Five research projects in the TOPICS-MDS database with data of both older person and informal caregiver at baseline and after 12 months follow-up were selected. Frailty was measured in five health domains (functional limitations, psychological well-being, social functioning, health-related quality of life, self-rated health). Care-related quality of life was measured with the Care-Related Quality of Life instrument (CarerQoL-7D), containing two positive (fulfilment, perceived support) and five negative dimensions (relational problems, mental health problems, physical health problems, financial problems, problems combining informal care with daily activities). RESULTS: 660 older person/caregiver couples were included. Older persons were on average 79 (SD 6.9) years of age, and 61% was female. Caregivers were on average 65 (SD 12.6) years of age, and 68% was female. Results of the multivariable linear and logistic regression analyses showed that an increase in older person's frailty over time was related to a lower total care-related quality of life of the caregiver, and to more mental and physical health problems, and problems with combining informal care with daily activities at follow-up. A change in the older person's psychological well-being was most important for the caregiver's care-related quality of life, compared to the other health domains. CONCLUSIONS: Health professionals observing decreasing psychological well-being of an older person and increasing hours of informal care provision should be aware of the considerable problems this may bring to their informal caregiver, and should tailor interventions to support informal caregivers according to their specific needs and problems.

The dual role of friendship and antipathy relations in the marginalization of overweight children in their peer networks: The TRAILS Study.

Weight-based stigma compromises the social networks of overweight children. To date, research on the position of overweight children in their peer network has focused only on friendship relations, and not on negative relationship dimensions. This study examined how overweight was associated with relations of friendship and dislike (antipathies) in the peer group. Exponential random graph models (ERGM) were used to examine friendship and antipathy relations among overweight children and their classmates, using a sub-sample from the TRacking Adolescents' Individual Lives Survey (N = 504, M age 11.4). Findings showed that overweight children were less likely to receive friendship nominations, and were more likely to receive dislike nominations. Overweight children were also more likely than their non-overweight peers to nominate classmates that they disliked. Together, the results indicate that positive and negative peer relations are impacted by children's weight status, and are relevant to addressing the social marginalization of overweight children.

Long-term exposure to road traffic noise, ambient air pollution, and cardiovascular risk factors in the HUNT and lifelines cohorts.

AIMS: Blood biochemistry may provide information on associations between road traffic noise, air pollution, and cardiovascular disease risk. We evaluated this in two large European cohorts (HUNT3, Lifelines). METHODS AND RESULTS: Road traffic noise exposure was modelled for 2009 using a simplified version of the Common Noise Assessment Methods in Europe (CNOSSOS-EU). Annual ambient air pollution (PM10, NO2) at residence was estimated for 2007 using a Land Use Regression model. The statistical platform DataSHIELD was used to pool data from 144 082 participants aged ≥20 years to enable individual-level analysis. Generalized linear models were fitted to assess cross-sectional associations between pollutants and high-sensitivity C-reactive protein (hsCRP), blood lipids and for (Lifelines only) fasting blood glucose, for samples taken during recruitment in 2006-2013. Pooling both cohorts, an inter-quartile range (IQR) higher day-time noise (5.1 dB(A)) was associated with 1.1% [95% confidence interval (95% CI: 0.02-2.2%)] higher hsCRP, 0.7% (95% CI: 0.3-1.1%) higher triglycerides, and 0.5% (95% CI: 0.3-0.7%) higher high-density lipoprotein (HDL); only the association with HDL was robust to adjustment for air pollution. An IQR higher PM10 (2.0 µg/m3) or NO2 (7.4 µg/m3) was associated with higher triglycerides (1.9%, 95% CI: 1.5-2.4% and 2.2%, 95% CI: 1.6-2.7%), independent of adjustment for noise. Additionally for NO2, a significant association with hsCRP (1.9%, 95% CI: 0.5-3.3%) was seen. In Lifelines, an IQR higher noise (4.2 dB(A)) and PM10 (2.4 µg/m3) was associated with 0.2% (95% CI: 0.1-0.3%) and 0.6% (95% CI: 0.4-0.7%) higher fasting glucose respectively, with both remaining robust to adjustment for air/noise pollution. CONCLUSION: Long-term exposures to road traffic noise and ambient air pollution were associated with blood biochemistry, providing a possible link between road traffic noise/air pollution and cardio-metabolic disease risk.

Missing heritability: is the gap closing? An analysis of 32 complex traits in the Lifelines Cohort Study.

Despite the recent explosive rise in number of genetic markers for complex disease traits identified in genome-wide association studies, there is still a large gap between the known heritability of these traits and the part explained by these markers. To gauge whether this 'heritability gap' is closing, we first identified genome-wide significant SNPs from the literature and performed replication analyses for 32 highly relevant traits from five broad disease areas in 13 436 subjects of the Lifelines Cohort. Next, we calculated the variance explained by multi-SNP genetic risk scores (GRSs) for each trait, and compared it to their broad- and narrow-sense heritabilities captured by all common SNPs. The majority of all previously-associated SNPs (median=75%) were significantly associated with their respective traits. All GRSs were significant, with unweighted GRSs generally explaining less phenotypic variance than weighted GRSs, for which the explained variance was highest for height (15.5%) and varied between 0.02 and 6.7% for the other traits. Broad-sense common-SNP heritability estimates were significant for all traits, with the additive effect of common SNPs explaining 48.9% of the variance for height and between 5.6 and 39.2% for the other traits. Dominance effects were uniformly small (0-1.5%) and not significant. On average, the variance explained by the weighted GRSs accounted for only 10.7% of the common-SNP heritability of the 32 traits. These results indicate that GRSs may not yet be ready for accurate personalized prediction of complex disease traits limiting widespread adoption in clinical practice.

Factors of physical activity among Chinese children and adolescents: a systematic review.

BACKGROUND: Lack of physical activity is a growing problem in China, due to the fast economic development and changing living environment over the past two decades. The aim of this review is to summarize the factors related to physical activity in Chinese children and adolescents during this distinct period of development. METHODS: A systematic search was finished on Jan 10th, 2017, and identified 2200 hits through PubMed and Web of Science. English-language published studies were included if they reported statistical associations between factors and physical activity. Adapted criteria from the Strengthening The Reporting of OBservational studies in Epidemiology (STROBE) statement and evaluation of the quality of prognosis studies in systematic reviews (QUIPS) were used to assess the risk of bias of the included studies. Related factors that were reported in at least three studies were summarized separately for children and adolescents using a semi-quantitative method. RESULTS: Forty two papers (published 2002-2016) were included. Most designs were cross-sectional (79%), and most studies used questionnaires to assess physical activity. Sample size was above 1000 in 18 papers (43%). Thirty seven studies (88%) showed acceptable quality by methodological quality assessment. Most studies reported a low level of physical activity. Boys were consistently more active than girls, the parental physical activity was positively associated with children and adolescents' physical activity, children in suburban/rural regions showed less activity than in urban regions, and, specifically in adolescents, self-efficacy was positively associated with physical activity. Family socioeconomic status and parental education were not associated with physical activity in children and adolescents. CONCLUSIONS: The studies included in this review were large but mostly of low quality in terms of study design (cross-sectional) and methods (questionnaires). Parental physical activity and self-efficacy are promising targets for future physical activity promotion programmes. The low level of physical activity raises concern, especially in suburban/rural regions. Future research is required to enhance our understanding of other influences, such as the physical environment, especially in early childhood.

Plasma N-terminal Prosomatostatin and Risk of Incident Cardiovascular Disease and All-Cause Mortality in a Prospective Observational Cohort: the PREVEND Study.

BACKGROUND: Somatostatin is a component of the well-known insulin-like growth factor-1/growth hormone (GH) longevity axis. There is observational evidence that increased GH is associated with an increased risk of cardiovascular disease (CVD). We aimed to investigate the potential association of plasma N-terminal fragment prosomatostatin (NT-proSST) with incident CVD and all-cause mortality in apparently healthy adults. METHODS: We studied 8134 participants without history of CVD (aged 28-75 years; women, 52.6%) from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study in Groningen, the Netherlands. Plasma NT-proSST was measured in baseline samples. Outcomes were incidence of CVD and all-cause mortality. RESULTS: In cross-sectional analyses, NT-proSST [mean (SD), 384.0 (169.3) pmol/L] was positively associated with male sex and age (both P < 0.001). During a median follow-up of 10.5 (Q1-Q3: 9.9-10.8) years, 708 (8.7%) participants developed CVD and 517 (6.4%) participants died. In univariable analyses, NT-proSST was associated with an increased risk of incident CVD and all-cause mortality (both P < 0.001). In multivariable analyses, these associations were independent of the Framingham risk factors, with hazard ratios (95% CI) per doubling of NT-proSST of 1.17 (1.03-1.34; P = 0.02) for incident CVD and of 1.28 (1.09-1.49; P = 0.002) for all-cause mortality. Addition of NT-proSST to the updated Framingham Risk Score improved reclassification (integrated discrimination improvement (P < 0.001); net reclassification improvement was 2.5% (P = 0.04)). CONCLUSIONS: Plasma NT-proSST is positively associated with increased risk of future CVD and all-cause mortality, partly independent of traditional CVD risk factors. Further research is needed to address the nature of associations.

Maelstrom Research guidelines for rigorous retrospective data harmonization.

Background: It is widely accepted and acknowledged that data harmonization is crucial: in its absence, the co-analysis of major tranches of high quality extant data is liable to inefficiency or error. However, despite its widespread practice, no formalized/systematic guidelines exist to ensure high quality retrospective data harmonization. Methods: To better understand real-world harmonization practices and facilitate development of formal guidelines, three interrelated initiatives were undertaken between 2006 and 2015. They included a phone survey with 34 major international research initiatives, a series of workshops with experts, and case studies applying the proposed guidelines. Results: A wide range of projects use retrospective harmonization to support their research activities but even when appropriate approaches are used, the terminologies, procedures, technologies and methods adopted vary markedly. The generic guidelines outlined in this article delineate the essentials required and describe an interdependent step-by-step approach to harmonization: 0) define the research question, objectives and protocol; 1) assemble pre-existing knowledge and select studies; 2) define targeted variables and evaluate harmonization potential; 3) process data; 4) estimate quality of the harmonized dataset(s) generated; and 5) disseminate and preserve final harmonization products. Conclusions: This manuscript provides guidelines aiming to encourage rigorous and effective approaches to harmonization which are comprehensively and transparently documented and straightforward to interpret and implement. This can be seen as a key step towards implementing guiding principles analogous to those that are well recognised as being essential in securing the foundational underpinning of systematic reviews and the meta-analysis of clinical trials.

The LifeLines Cohort Study: Prevalence and treatment of cardiovascular disease and risk factors.

BACKGROUND: The LifeLines Cohort Study is a large three-generation prospective study and Biobank. Recruitment and data collection started in 2006 and follow-up is planned for 30years. The central aim of LifeLines is to understand healthy ageing in the 21st century. Here, the study design, methods, baseline and major cardiovascular phenotypes of the LifeLines Cohort Study are presented. METHODS AND RESULTS: Baseline cardiovascular phenotypes were defined in 9700 juvenile (8-18years) and 152,180 adult (≥18years) participants. Cardiovascular disease (CVD) was defined using ICD-10 criteria. At least one cardiovascular risk factor was present in 73% of the adult participants. The prevalence, adjusted for the Dutch population, was determined for risk factors (hypertension (33%), hypercholesterolemia (19%), diabetes (4%), overweight (56%), and current smoking (19%)) and CVD (myocardial infarction (1.8%), heart failure (1.0%), and atrial fibrillation (1.3%)). Overall CVD prevalence increased with age from 9% in participants<65years to 28% in participants≥65years. Of the participants with hypertension, hypercholesterolemia and diabetes, respectively 75%, 96% and 41% did not receive preventive pharmacotherapy. CONCLUSIONS: The contemporary LifeLines Cohort Study provides researchers with unique and novel opportunities to study environmental, phenotypic, and genetic risk factors for CVD and is expected to improve our knowledge on healthy ageing. In this contemporary Western cohort we identified a remarkable high percentage of untreated CVD risk factors suggesting that not all opportunities to reduce the CVD burden are utilised.