Early imaging biomarkers of lung cancer, COPD and coronary artery disease in the general population: rationale and design of the ImaLife (Imaging in Lifelines) Study.

Lung cancer, chronic obstructive pulmonary disease (COPD), and coronary artery disease (CAD) are expected to cause most deaths by 2050. State-of-the-art computed tomography (CT) allows early detection of lung cancer and simultaneous evaluation of imaging biomarkers for the early stages of COPD, based on pulmonary density and bronchial wall thickness, and of CAD, based on the coronary artery calcium score (CACS), at low radiation dose. To determine cut-off values for positive tests for elevated risk and presence of disease is one of the major tasks before considering implementation of CT screening in a general population. The ImaLife (Imaging in Lifelines) study, embedded in the Lifelines study, is designed to establish the reference values of the imaging biomarkers for the big three diseases in a well-defined general population aged 45 years and older. In total, 12,000 participants will undergo CACS and chest acquisitions with latest CT technology. The estimated percentage of individuals with lung nodules needing further workup is around 1-2%. Given the around 10% prevalence of COPD and CAD in the general population, the expected number of COPD and CAD is around 1000 each. So far, nearly 4000 participants have been included. The ImaLife study will allow differentiation between normal aging of the pulmonary and cardiovascular system and early stages of the big three diseases based on low-dose CT imaging. This information can be finally integrated into personalized precision health strategies in the general population.

Patient attitudes towards faecal sampling for gut microbiome studies and clinical care reveal positive engagement and room for improvement.

Faecal sample collection is crucial for gut microbiome research and its clinical applications. However, while patients and healthy volunteers are routinely asked to provide stool samples, their attitudes towards sampling remain largely unknown. Here, we investigate the attitudes of 780 Dutch patients, including participants in a large Inflammatory Bowel Disease (IBD) gut microbiome cohort and population controls, in order to identify barriers to sample collection and provide recommendations for gut microbiome researchers and clinicians. We sent questionnaires to 660 IBD patients and 112 patients with other disorders who had previously been approached to participate in gut microbiome studies. We also conducted 478 brief interviews with participants in our general population cohort who had collected stool samples. Statistical analysis of the data was performed using R. 97.4% of respondents reported that they had willingly participated in stool sample collection for gut microbiome research, and most respondents (82.9%) and interviewees (95.6%) indicated willingness to participate again, with their motivations for participating being mainly altruistic (57.0%). Responses indicated that storing stool samples in the home freezer for a prolonged time was the main barrier to participation (52.6%), but clear explanations of the sampling procedures and their purpose increased participant willingness to collect and freeze samples (P = 0.046, P = 0.003). To account for participant concerns, gut microbiome researchers establishing cohorts and clinicians trying new faecal tests should provide clear instructions, explain the rationale behind their protocol, consider providing a small freezer and inform patients about study outcomes. By assessing the attitudes, motives and barriers surrounding participation in faecal sample collection, we provide important information that will contribute to the success of gut microbiome research and its near-future clinical applications.

Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis.

We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including ≥100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1-100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40-69 years, 55.5% female) from the United Kingdom and 409,617 people (≥18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the 'acceptable' sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8-10 h and 18% report daytime sleepiness. In adults (≥18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6-19.4%) were more prevalent than short sleep duration (6.5% with TST < 6 h). Insomnia symptoms were most frequent in people spending ≥9 h in bed, whereas poor sleep quality was more frequent in those spending <6 h in bed. TST was similar across countries, but insomnia symptoms were 1.5-2.9 times higher in the United States. Women (≥41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.

Prevalence and Accuracy of Information on CYP2D6, CYP2C19, and CYP2C9 Related Substrate and Inhibitor Co-Prescriptions in the General Population: A Cross-Sectional Descriptive Study as Part of the PharmLines Initiative.

BACKGROUND: Drug-drug interaction (DDI) is one of the main contributors to adverse drug reactions and therefore, it is important to study its frequency in the population. We aimed to investigate frequency and concordance on CYP2D6, CYP2C19, and CYP2C9 (CYP2D6/2C19/2C9)-mediated potential DDIs at the Lifelines cohort and linked data from the pharmacy database IADB.nl. METHODS: As part of the University of Groningen PharmLines Initiative, data were collected on CYP2D6/2C19/2C9-related substrate/inhibitors from entry questionnaires of Lifelines participants and linked information from the pharmacy database IADB.nl. CYP2D6/2C19/2C9 related co-prescriptions were divided based on the type of drugs i.e. chronically used medication (CM) or occasionally used medication (OM). This resulted in the combination of two chronically used drugs (CM-CM), chronically and occasionally used medication (CM-OM), and two occasionally used drugs (OM-OM). To measure the agreement level, cohen's kappa statistics and test characteristics were used. Results were stratified by time window, gender, and age. RESULTS: Among 80,837 medicine users in the Lifelines, about 1-2 per hundred participants were exposed to a CYP2D6/2C19/2C9-mediated potential DDI. Overall, the overlapping time window of three months produced the highest mean kappa values between the databases i.e. 0.545 (95% CI:0.544-0.545), 0.512 (95% CI:0.511-0.512), and 0.374 (95% CI:0.373-0.375), respectively. CM-CM had a better level of agreement (good) than CM-OM (fair to moderate) and OM-OM combination (poor to moderate). The influence of gender on concordance values was different for different CYPs. Among older persons, agreement levels were higher than for the younger population. CONCLUSIONS: CYP2D6/2C19/2C9-mediated potential DDIs were frequent and concordance of data varied by time window, type of combination, sex and age. Subsequent studies should rather use a combination of self-reported and pharmacy database information.

Concordance assessment of self-reported medication use in the Netherlands three-generation Lifelines Cohort study with the pharmacy database iaDB.nl: The PharmLines initiative.

BACKGROUND: While self-reported data are commonly used as a source of medication use for pharmaco-epidemiological studies, such information is prone to forms of bias. Several previous studies showed that various factors like age, type of drug and data collection method may influence accuracy. We aimed to assess the concordance of the self-reported medication use that was documented at entry to the Lifelines Cohort Study, a three-generation follow-up study in the Netherlands that started in 2006 and included over 167,000 participants. MATERIALS AND METHODS: As part of the PharmLines Initiative, we collected medication data from the Lifelines participants encoded according to the Anatomical Therapeutic Chemical (ATC) coding scheme and linked the data via Statistics Netherlands to the widely used and representative pharmacy prescription database of the University of Groningen, IADB.nl. Analyses were conducted at second level of ATC coding for all recorded medications as well as a top list of most used medications at drug-specific fifth level. Cohen's kappa statistics were used to measure the concordance for all participants according to sex and age. RESULTS: The level of concordance between the two data sources largely differed according to the therapeutic class. Medication used for the cardiovascular system and diabetes, thyroid therapy, bisphosphonates and anti-thrombotic drugs showed a very good agreement (κ>0.75). Medication as needed or prone to stigmatization bias showed a moderate agreement (κ=0.41-0.60), whereas medications used for short periods of time showed a fair agreement (κ=0.0-0.4). Concordance was similar for males and females, but younger adults tended to have lower concordance rates than older adults. CONCLUSION: The self-reported method was valid for capturing prevalent chronic medication use at one moment in time, but invalid for medication used for short periods of time. There is no effect of sex on the agreement, and more studies are needed on the influence of age. Future pharmaco-epidemiological studies should preferably combine the two data sources to achieve the highest accuracy of drug exposure rates.

Cohort Profile: LifeLines, a three-generation cohort study and biobank.

The LifeLines Cohort Study is a large population-based cohort study and biobank that was established as a resource for research on complex interactions between environmental, phenotypic and genomic factors in the development of chronic diseases and healthy ageing. Between 2006 and 2013, inhabitants of the northern part of The Netherlands and their families were invited to participate, thereby contributing to a three-generation design. Participants visited one of the LifeLines research sites for a physical examination, including lung function, ECG and cognition tests, and completed extensive questionnaires. Baseline data were collected for 167 729 participants, aged from 6 months to 93 years. Follow-up visits are scheduled every 5 years, and in between participants receive follow-up questionnaires. Linkage is being established with medical registries and environmental data. LifeLines contains information on biochemistry, medical history, psychosocial characteristics, lifestyle and more. Genomic data are available including genome-wide genetic data of 15 638 participants. Fasting blood and 24-h urine samples are processed on the day of collection and stored at -80 °C in a fully automated storage facility. The aim of LifeLines is to be a resource for the national and international scientific community. Requests for data and biomaterials can be submitted to the LifeLines Research Office [LLscience@umcg.nl].

Measuring alcohol use: "quantity frequency variability" and "weekly recall" compared among Turks and Moroccans in the Netherlands.

The aim of the present study was to test the quality of the "Quantity Frequency Variability" (QFV) measure and the "Weekly Recall" (WR) measure among second-generation Turks and Moroccans in The Netherlands. Data were gathered in an experimental study conducted in 2002, in Rotterdam, the second largest city in the Netherlands. A sample of 744 second-generation Turks and 753 second-generation Moroccans, aged 16 years and older, was approached to participate in the study. The response rate was 40.3% among Turks and 37.5% among Moroccans, which resulted in 300 Turks (mean age 21.8, of which 51.7% were male) and 282 Moroccans (mean age 20.1, of which 44.9% were male) participating in the experimental study. Differences in item non-response rates and alcohol reports between both measures were analyzed among the drinking sample; i.e., 95 Turks (31.7%) and 26 Moroccans (9.2%). Data showed higher alcohol reports with the QFV measure compared to the WR measure. Furthermore, item non-response rates were significantly lower for the QFV measure compared to the WR measure. The results suggest that, compared to the WR measure, the QFV measure is a more appropriate instrument to study the prevalence of alcohol use among second-generation Turks and Moroccans. Limitations of the study are discussed.

The effect of data collection mode and ethnicity of interviewer on response rates and self-reported alcohol use among Turks and Moroccans in the Netherlands: an experimental study.

AIMS: To test the effects of data collection mode and ethnicity of interviewers on response rates and self-reported alcohol use among second-generation Turks and Moroccans in Rotterdam, The Netherlands. METHODS: Two hundred and sixty-nine Turks and 271 Moroccans were interviewed face-to-face, and 475 Turks and 482 Moroccans received a mailed questionnaire. Half of the Turks and Moroccans randomly allocated to the interview mode were ethnically matched to the interviewer; the remainder were allocated to a Dutch interviewer. RESULTS: Turks and Moroccans more often responded to a face-to-face interview than to a mailed questionnaire. No effect of ethnicity of interviewer on response rates was demonstrated. With respect to the effects on alcohol reports, Turks and Moroccans tended to report a higher alcohol use in the mailed survey than in the face-to-face interview. They reported significantly more often excessive drinking in the mail survey than in the face-to-face interviews. Ethnicity of the interviewer resulted in Turks and Moroccans reporting a higher prevalence of alcohol use during the previous 6 months when interviewed by a Dutch interviewer compared with an ethnically matched interviewer. CONCLUSIONS: Among second-generation Turks and Moroccans, mail surveys seem most suitable to measure mean and excessive alcohol use. However, interviews held by Dutch interviewers seem to be the most appropriate method to study the prevalence of alcohol use during the previous 6 months.

Correlates of stages of change of smoking among inhabitants of deprived neighbourhoods.

BACKGROUND: This study examines the prevalence and correlates of stages of change of smoking, in terms of psychosocial, structural and sociodemographic factors, among inhabitants of deprived neighbourhoods. METHODS: Cross-sectional data were obtained from a survey on health related behaviour. Subjects were 2009 current and former smokers, aged 20-46, living in deprived neighbourhoods in Rotterdam, the second largest city in the Netherlands. Three groups of smokers were formed according to the stages of change-definitions of the Transtheoretical Model: smokers not planning to quit (precontemplators), smokers planning to quit (contemplators/preparators) and former smokers (actors/maintainers). Smokers planning to quit and smokers not planning to quit were compared regarding psychosocial factors (attitude, social norm, self-efficacy), structural factors (neighbourhood problems, material deprivation, financial problems, employment status) and sociodemographic factors (age, gender, marital status, cultural background, educational level). Former smokers were compared with smokers planning to quit regarding structural and sociodemographic factors. Logistic regression was used to assess correlates of stages of change. RESULTS: Smokers planning to quit (prevalence = 19%) reported a more positive attitude, stronger social norms and higher self-efficacy expectations in quitting smoking than smokers not planning to quit (prevalence = 57%). Smokers planning to quit less often were Dutch-born, more often had attended higher vocational schooling or university and more often reported experiencing two or more neighbourhood problems compared to smokers not planning to quit. Former smokers (prevalence = 24%) were older, more often Dutch-born, married, employed and higher educated, compared to smokers planning to quit. Furthermore, former smokers less often reported material deprivation and financial problems than smokers planning to quit. CONCLUSION: Among people living in deprived neighbourhoods, different factors correlate with different stages of change of smoking. Implications for health promotion are discussed.

Methodological problems related to alcohol research among Turks and Moroccans living in the Netherlands: findings from semi-structured interviews.

OBJECTIVES: To identify factors related to alcohol use among Turks and Moroccans living in the Netherlands. Furthermore, to reveal methodological problems related to research among Turks and Moroccans in general and to alcohol research among these groups in particular. DESIGN: Individual face-to-face interviews were carried out with Dutch researchers (n = 9), Turkish and Moroccan (health) practitioners working in the field with Turks (n = 4) or Moroccans (n = 2), and members of the target population with a Turkish (n = 3) or a Moroccan background (n = 2). Furthermore, focus-group interviews were held with Turkish women (n = 4), Turkish men (n = 3), Moroccan women (n = 4) and Moroccan men (n = 3) working as health professionals. RESULTS: Alcohol use seems prevalent particularly among second-generation Turks and Moroccans and is related to: upbringing, influence of peer groups, integration and the degree in which Islamic rules are practised. Written questionnaires seem more appropriate for second-generation Turks and Moroccans, because they have fewer language problems and are more familiar with Western bureaucratic society. However, both generations may prefer face-to-face interviews since both groups fear that 'written' answers about the sensitive subject 'alcohol use' may somehow become known among community members. Similarly, an interviewer with a Dutch background may elicit more reliable answers about alcohol use than an interviewer with a Turkish or Moroccan background. CONCLUSION: In alcohol research special attention should be paid to second-generation Turks and Moroccans. Although it is probably easier to conduct alcohol studies in this group than in first-generation Turks and Moroccans, quantitative research is needed to test the hypothesis that written questionnaires elicit more reliable answers about alcohol use than face-to-face interviews. Furthermore, the influence of ethnic matching on response and data quality should be tested further.