Wolfgang Ahrens

Handbook of epidemiology

Preliminary Contents Preface - Wolfgang Ahrens, Iris Pigeot.Foreword - John M. Last.Introduction - Wolfgang Ahrens, Klaus Krickeberg, Iris Pigeot.1. Concepts and Methodological Approaches in Epidemiology 1.1. Basic Concepts - Kenneth J. Rothman, Sander Greenland1.2. Risk Measures - Jacques Benichou, Mari Palta1.3. Descriptive Studies - Donald M. Parkin, Freddie Bray1.4. Use of Routine Data and Disease Registries - Mans Rosen, Timo Hakulinen 1.5. Cohort Studies - Anthony B. Miller, David C. Goff Jr. Karin Bammann, Pascal Wild1.6. Case Control Studies - Norman E. Breslow1.7. Modern Study Designs - Philip H. Kass, Ellen B. Gold1.8. Intervention Trials - Silvia Franceschi, Martyn Plummer1.9. Confounding and Interaction - Neal Pearce, Sander Greenland1.10. Epidemiological Field Work in Population-Based Studies - Arlene Fink1.11. Exposure Assessment - Sylvaine Cordier, Patricia Stewart1.12. Design and Planning of Epidemiological Studies - Pascal Wild1.13. Quality Control and Good Epidemiological Practice - Preetha Rajaraman, Jonathan M. Samet 2. Statistical Methods in Epidemiology 2.1. Sample Size Determination in Epidemiologic Studies- Janet D. Elashoff, Stanley Lemeshow2.2. General Principles of Data Analysis - Heiko Becher2.3. Regression Mehtods for Epidemiologic Analysis - Sander Greenland2.4. Survival Analysis - Peter Sasieni2.5. Measurement Error - Jeffrey S. Buzas, Leonard A. Stefanski, Tor D. Tosteson2.6. Missing Data - Geert Molenberghs, Caroline Beunckens, Ivy Jansen, Herbert Thijs, Geert Verbeke, Michael G. Kenward2.7. Meta Analysis - Maria Blettner, Peter Schlattmann 2.8. Geographical Epidemiology - John F. Bithell3. Applications in Epidemiology 3.1. Social Epidemiology - Tarani Chandola, Michael Marmot3.2. Occupational Epidemiology - Franco Merletti, Dario Mirabelli, Lorenzo Richiardi 3.3. Environmental Epidemiology - Lothar Kreienbrock3.4. Nutritional Epidemiology - Dorothy Mackerras, Barrie M. Margetts3.5. Reproductive Epidemiology - JAA rn Olsen, Olga Basso3.6. Molecular Epidemiology - Paolo Vineis, Guiseppe Matullo, Marianne Berwick3.7. Genetic Epidemiology - Heike Bickeboller3.8. Clinical Epidemiology - Holger J. Schunemann, Gordon H. Guyatt 3.9. Pharmacoepidemiology - Edeltraut Garbe, Samy Suissa 3.10. Screening - Anthony B. Miller3.11. Prevention and Health Promotion - John W. Farquhar, Stephen P. Fortmann4. Research Areas in Epidemiology 4.1. Infectious Diseases - Susanne Straif-Bourgois, Raoult Ratard 4.2. Cardiovascular Diseases - Darwin R. Labarthe4.3. Cancer Epidemiology - Paolo Boffetta4.4. Musculoskeletal Disorders - Hilkka Riihimaki4.5. Health Systems Research - Thomas Schafer, Christian Gericke, Reinhard Busse4.6. Epidemiology in Developing Countries Part A: Klaus Krickeberg, Part B: Anita Kar, Asit Kumar Chakraborty4.7. Ethical Aspects of Epidemiological Research - Hubert G. Leufkens, Johannes J.M. van Delden

Physical fitness reference standards in European children: the IDEFICS study

Background/Objectives:A low fitness status during childhood and adolescence is associated with important health-related outcomes, such as increased future risk for obesity and cardiovascular diseases, impaired skeletal health, reduced quality of life and poor mental health. Fitness reference values for adolescents from different countries have been published, but there is a scarcity of reference values for pre-pubertal children in Europe, using harmonised measures of fitness in the literature. The IDEFICS study offers a good opportunity to establish normative values of a large set of fitness components from eight European countries using common and well-standardised methods in a large sample of children. Therefore, the aim of this study is to report sex- and age-specific fitness reference standards in European children.Subjects/Methods:Children (10u2009302) aged 6–10.9 years (50.7% girls) were examined. The test battery included: the flamingo balance test, back-saver sit-and-reach test (flexibility), handgrip strength test, standing long jump test (lower-limb explosive strength) and 40-m sprint test (speed). Moreover, cardiorespiratory fitness was assessed by a 20-m shuttle run test. Percentile curves for the 1st, 3rd, 10th, 25th, 50th, 75th, 90th, 97th and 99th percentiles were calculated using the General Additive Model for Location Scale and Shape (GAMLSS).Results:Our results show that boys performed better than girls in speed, lower- and upper-limb strength and cardiorespiratory fitness, and girls performed better in balance and flexibility. Older children performed better than younger children, except for cardiorespiratory fitness in boys and flexibility in girls.Conclusions:Our results provide for the first time sex- and age-specific physical fitness reference standards in European children aged 6–10.9 years.

The German National Cohort: Aims, study des

The German National Cohort (GNC) is a joint interdisciplinary endeavour of scientists from the Helmholtz and the Leibniz Association, universities, and other research institutes. Its aim is to investigate the causes for the development of major chronic diseases, i.e. cardiovascular diseases, cancer, diabetes, neurodegenerative/-psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases, and their pre-clinical stages or functional health impairments. Across Germany, a random sample of the general population will be drawn by 18 regional study centres, including a total of 100,000 women and 100,000 men aged 20–69xa0years. The baseline assessments include an extensive interview and self-completion questionnaires, a wide range of medical examinations and the collection of various biomaterials. In a random subgroup of 20xa0% of the participants (nxa0=xa040,000) an intensified examination (“Level 2”) programme will be performed. In addition, in five of the 18 study centres a total of 30,000 study participants will take part in a magnetic resonance imaging examination programme, and all of these participants will also be offered the intensified Level 2 examinations. After 4–5xa0years, all participants will be invited for a re-assessment. Information about chronic disease endpoints will be collected through a combination of active follow-up (including questionnaires every 2–3xa0years) and record linkages. The GNC is planned for an overall duration of 25–30xa0years. It will provide a major, central resource for population-based epidemiology in Germany, and will help to identify new and tailored strategies for early detection, prediction, and primary prevention of major diseases.

Agreement of different methods for assessing sleep characteristics: a comparison of two actigraphs, wrist and hip placement, and self-report with polysomnography

OBJECTIVEnTo assess the agreement of sleep parameters measured by two actigraphs (SOMNOwatch plus, ActiGraph GT3X+) at two different placements (wrist, hip) and of self-reported sleep with polysomnography (PSG).nnnMETHODSnWe estimated agreement with PSG for total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), number of awakenings after sleep onset (NASO), and sleep efficiency (SE%) for 100 participants of the general population, aged 18-75 years by judging mean differences to PSG and intervals of agreement using Bland-Altman plots.nnnRESULTSnMean difference to PSG for TST was 8.3u2009min (95% confidence intervals [CI] -7.4; 24.1) for SOMNOwatch plus (wrist), 39.8u2009min (95% CI 24.3; 55.3) for self-report, -79.0u2009min (95% CI -89.0; -68.9) for SOMNOwatch plus (hip), and -81.1u2009min (95% CI -91.9; -70.4) for GT3X+ (hip), respectively. The width of intervals of agreement differed with the placement of the devices. Mean differences to PSG were higher for hip-based measurements compared with wrist placement for most parameters.nnnCONCLUSIONSnAgreement of sleep parameters assessed by actigraphy with PSG differs with the placement of the device and is limited for hip-based measurements. Agreement of self-report with PSG is comparable to that of actigraphy for some parameters.

Towards the integration and development of a cross-European research network and infrastructure: the DEterminants of DIet and Physical ACtivity (DEDIPAC) Knowledge Hub

To address major societal challenges and enhance cooperation in research across Europe, the European Commission has initiated and facilitated `joint programming’. Joint programming is a process by which Member States engage in defining, developing and implementing a common strategic research agenda, based on a shared vision of how to address major societal challenges that no Member State is capable of resolving independently. Setting up a Joint Programming Initiative (JPI) should also contribute to avoiding unnecessary overlap and repetition of research, and enable and enhance the development and use of standardised research methods, procedures and data management. The Determinants of Diet and Physical Activity (DEDIPAC) Knowledge Hub (KH) is the first act of the European JPI `A Healthy Diet for a Healthy Life’. The objective of DEDIPAC is to contribute to improving understanding of the determinants of dietary, physical activity and sedentary behaviours. DEDIPAC KH is a multi-disciplinary consortium of 46 consortia and organisations supported by joint programming grants from 12 countries across Europe. The work is divided into three thematic areas: (I) assessment and harmonisation of methods for future research, surveillance and monitoring, and for evaluation of interventions and policies; (II) determinants of dietary, physical activity and sedentary behaviours across the life course and in vulnerable groups; and (III) evaluation and benchmarking of public health and policy interventions aimed at improving dietary, physical activity and sedentary behaviours. In the first three years, DEDIPAC KH will organise, develop, share and harmonise expertise, methods, measures, data and other infrastructure. This should further European research and improve the broad multi-disciplinary approach needed to study the interactions between multilevel determinants in influencing dietary, physical activity and sedentary behaviours. Insights will be translated into more effective interventions and policies for the promotion of healthier behaviours and more effective monitoring and evaluation of the impacts of such interventions.

Incidence of high blood pressure in children — Effects of physical activity and sedentary behaviors: The IDEFICS study High blood pressure, lifestyle and children

BACKGROUND/OBJECTIVESnHigh blood pressure (HBP) is one of the most important risk factors for cardiovascular diseases and it has a high prevalence in pediatric populations. However, the determinants of the incidence of Pre-HBP and HBP in children are not well known. i) To describe the incidence of HBP in European children; and ii) to evaluate the effect of physical activity (PA) and sedentary behavior (SB) on the Pre-HBP and HBP.nnnMETHODSnThe IDEFICS cohort study. A total of 16,228 children 2-9years at baseline were recruited by complex sampling population-based survey in eight European countries. At baseline (T0), 5221 children were selected for accelerometer measurements; 5061 children were re-examined 2years later (T1). We estimated the incidence of Pre-HBP and HBP and evaluate the effect of PA and SB on the Pre-HBP and HBP, by computing relative risks and the corresponding 95% confidence intervals (RR, 95% CI).nnnRESULTSnIncidences of Pre-HBP and HBP per year were: 121/1000 children and 110/1000 children, respectively. We found that children maintaining SB>2h/d during the two year follow-up showed a RR of having HBP of 1.28 (1.03-1.60). Children in T1 not performing the recommended amount of PA (<60min/d) have a RR of HBP of 1.53 (1.12 to 2.09). We found no association between pre-HBP and the behaviors.nnnCONCLUSIONnThe incidence of pre-HBP and HBP is high in European children. Maintaining sedentary behaviors during childhood increases the risk of developing HBP after two years of follow-up.

Human Papillomavirus 16 E6 Antibodies in Individuals without Diagnosed Cancer: A Pooled Analysis

Background: The increasing incidence of oropharyngeal cancer in many developed countries has been attributed to human papillomavirus type 16 (HPV16) infections. Recently, HPV16 E6 serology has been identified as a promising early marker for oropharyngeal cancer. Therefore, characterization of HPV16 E6 seropositivity among individuals without cancer is warranted. Methods: A total of 4,666 controls were pooled from several studies of cancer and HPV seropositivity, all tested within the same laboratory. HPV16 E6 seropositive controls were classified as having (i) moderate [mean fluorescent intensity (MFI) ≥ 484 and <1,000] or (ii) high seroreactivity (MFI ≥ 1,000). Associations of moderate and high HPV16 E6 seroreactivity with (i) demographic risk factors; and seropositivity for (ii) other HPV16 proteins (E1, E2, E4, E7, and L1), and (iii) E6 proteins from non-HPV16 types (HPV6, 11, 18, 31, 33, 45, and 52) were evaluated. Results: Thirty-two (0.7%) HPV16 E6 seropositive controls were identified; 17 (0.4%) with moderate and 15 (0.3%) with high seroreactivity. High HPV16 E6 seroreactivity was associated with former smoking [odds ratio (OR), 5.5; 95% confidence interval (CI), 1.2–51.8], and seropositivity against HPV16 L1 (OR, 4.8; 95% CI, 1.3–15.4); E2 (OR, 7.7; 95% CI, 1.4–29.1); multiple HPV16 proteins (OR, 25.3; 95% CI, 2.6–119.6 for three HPV16 proteins beside E6) and HPV33 E6 (OR, 17.7; 95% CI, 1.9–81.8). No associations were observed with moderate HPV16 E6 seroreactivity. Conclusions: High HPV16 E6 seroreactivity is rare among individuals without diagnosed cancer and was not explained by demographic factors. Impact: Some HPV16 E6 seropositive individuals without diagnosed HPV-driven cancer, especially those with seropositivity against other HPV16 proteins, may harbor a biologically relevant HPV16 infection. Cancer Epidemiol Biomarkers Prev; 24(4); 683–9. ©2015 AACR.

Adult height and head and neck cancer: a pooled analysis within the INHANCE Consortium

Several epidemiological studies have shown a positive association between adult height and cancer incidence. The only study conducted among women on mouth and pharynx cancer risk, however, reported an inverse association. This study aims to investigate the association between height and the risk of head and neck cancer (HNC) within a large international consortium of HNC. We analyzed pooled individual-level data from 24 case–control studies participating in the International Head and Neck Cancer Epidemiology Consortium. Odds ratios (ORs) and 95xa0% confidence intervals (CIs) were estimated separately for men and women for associations between height and HNC risk. Educational level, tobacco smoking, and alcohol consumption were included in all regression models. Stratified analyses by HNC subsites were performed. This project included 17,666 cases and 28,198 controls. We found an inverse association between height and HNC (adjusted OR per 10xa0cm heightxa0=xa00.91, 95xa0% CI 0.86–0.95 for men; adjusted ORxa0=xa00.86, 95xa0% CI 0.79–0.93 for women). In men, the estimated OR did vary by educational level, smoking status, geographic area, and control source. No differences by subsites were detected. Adult height is inversely associated with HNC risk. As height can be considered a marker of childhood illness and low energy intake, the inverse association is consistent with prior studies showing that HNC occur more frequently among deprived individuals. Further studies designed to elucidate the mechanism of such association would be warranted.

Understanding the Links among neuromedin U Gene, beta2-adrenoceptor Gene and Bone Health: An Observational Study in European Children

Neuromedin U, encoded by the NMU gene, is a hypothalamic neuropeptide that regulates both energy metabolism and bone mass. The beta-2 adrenergic receptor, encoded by the ADRB2 gene, mediates several effects of catecholamine hormones and neurotransmitters in bone. We investigated whether NMU single nucleotide polymorphisms (SNPs) and haplotypes, as well as functional ADRB2 SNPs, are associated with bone stiffness in children from the IDEFICS cohort, also evaluating whether NMU and ADRB2 interact to affect this trait. A sample of 2,274 subjects (52.5% boys, age 6.2±1.8 years) from eight European countries, having data on calcaneus bone stiffness index (SI, mean of both feet) and genotyping (NMU gene: rs6827359, rs12500837, rs9999653; ADRB2 gene: rs1042713, rs1042714), was studied. After false discovery rate adjustment, SI was significantly associated with all NMU SNPs. rs6827359 CC homozygotes showed the strongest association (recessive model, Δu200a=u200a−1.8, pu200a=u200a0.006). Among the five retrieved haplotypes with frequencies higher than 1% (range 2.0–43.9%), the CCT haplotype (frequencyu200a=u200a39.7%) was associated with lower SI values (dominant model, Δu200a=u200a−1.0, pu200a=u200a0.04) as compared to the most prevalent haplotype. A non-significant decrease in SI was observed in in ADRB2 rs1042713 GG homozygotes, while subjects carrying SI-lowering genotypes at both SNPs (frequencyu200a=u200a8.4%) showed much lower SI than non-carriers (Δu200a=u200a−3.9, p<0.0001; p for interactionu200a=u200a0.025). The association was more evident in preschool girls, in whom SI showed a curvilinear trend across ages. In subgroup analyses, rs9999653 CC NMU or both GG ADRB2 genotypes were associated with either lower serum calcium or β-CrossLaps levels (pu200a=u200a0.01). This study in European children shows, for the first time in humans, a role for NMU gene through interaction with ADRB2 gene in bone strength regulation, more evident in preschool girls.

A Rare Truncating BRCA2 Variant and Genetic Susceptibility to Upper Aerodigestive Tract Cancer

Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10-10) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P het = .026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors.