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Zusammenfassung Einleitung Die positive Wirkung von Bewegung für die Gesundheit ist gut belegt. Dennoch scheinen städtische Maßnahmen zur Förderung der körperlichen Aktivität bisher nicht ausreichend erfolgreich umgesetzt zu werden. Ziel des vorliegenden Artikels ist die detaillierte Darstellung einer Bedarfsanalyse zur Förderung der körperlichen Aktivität im Rahmen des Projektes „Scientific Support Active City“ in Hamburg. Methodik In Anlehnung an den Intervention Mapping (IM) Ansatz wird zunächst eine systematische Bedarfsanalyse in fünf Schritten durchgeführt. Hierzu werden (1) Verantwortlichkeiten der Akteur*innen festgelegt, (2) Zielgruppen definiert und (3) verfügbare Datenquellen gesichtet, erfasst und geprüft. Auf dieser Basis sollen (4) Prävalenzen körperlicher Aktivität für die Zielgruppen dargestellt, (5) Ziele konkretisiert und erste Handlungsempfehlungen abgeleitet werden. Ergebnisse Nach Definition eines Kernteams sowie eines erweiterten Akteursnetzwerkes wurden für die Zielgruppen Kinder und Jugendliche, Erwachsene und ältere Erwachsene verfügbare Datenquellen identifiziert, die im Sinne eines Multi-Source Ansatzes zur Analyse des Bewegungsverhaltens genutzt werden können. Die zielgruppenspezifische Analyse verdeutlicht den Bedarf an weiteren repräsentativen Daten sowie Fördermaßnahmen z. B. für Frauen mit niedriger Bildung und Kindern aus sozio-ökonomisch schlechter gestellten Regionen. Schlussfolgerung Der IM-Ansatz hat sich in der Ausgestaltung der Bedarfsanalyse des Projektes „Scientific Support Active City“ als anwendbar erwiesen. Die initiierte Zusammenarbeit des Netzwerkes sowie der Evidenz basierte Ansatz zur Ableitung erster Bedarfe scheinen einen erfolgsversprechenden Ansatz zur Förderung der körperlichen Aktivität darzustellen. Eine langfristige städtische Gesamtstrategie für die Bewegungsförderung auf der Basis kooperativer wissensbasierter Zielfindung kann damit kurzfristige Einzelprojekte ablösen.

Objectives Oxysterols, a family of oxidized cholesterol derivates, are of increasing interest due to their role in cancer development and progression. Some oxysterols are estrogen receptor modulators and thus of particular interest in breast cancer research. In human studies, two forms of circulating oxysterols are commonly evaluated: “free” (unesterified) and “total” (esterified and unesterified). However, associations between free and total oxysterols are not well established. We addressed this knowledge gap in a pilot study by evaluating correlations between the free and the total form of each of the circulating oxysterols (free vs. total), and pairwise associations within the panel of total oxysterols (total vs. total) and the panel of free oxysterols (free vs. free). Methods Concentrations of oxysterols and other non-cholesterol sterols were quantified in blood samples of 27 breast cancer patients from the MARIE breast cancer patient cohort using liquid chromatography mass spectrometry. We used Spearman rank correlations to assess associations. Overall, 12 oxysterols (including 27-hydroxycholesterol (HC), 25-HC, 24S-HC, 7a-HC, 5a6a-epoxycholesterol) and five sterols (including lanosterol and desmosterol) were analyzed. Results Strong correlations (r≥0.82) were observed for seven circulating free and total oxysterols/sterols. The free and total form of 27-HC (r=0.63), 25-HC (r=0.54), and two more oxysterols were weaker correlated. Correlation patterns in the panel of total oxysterols/sterols and the panel of free oxysterols/sterols were similar. Conclusions These findings demonstrate that concentrations of most free and total oxysterols/sterols are strongly correlated. We provide further insight into the interrelationships between oxysterols in breast cancer patients.

Introduction: The causes of multiple sclerosis (MS) are not fully understood, yet. Genetic predisposition, environmental and lifestyle factors as well as an interplay thereof constitute relevant factors in the development of MS. Especially early-life risk factors such as having been breastfed may also be of relevance. Breast milk provides the newborn not only with essential nutrients and vitamins but also with numerous immune-active molecules, metabolites, oligosaccharides, and microbial components that are important for the development of the immune system. We present a systematic review and meta-analysis on the influence of having been breastfed during infancy on the risk of developing MS. Methods: The databases MEDLINE, Cochrane Library, and Web of Science were systematically searched for studies on breastfeeding and MS published between database inception and May 18, 2022. Observational studies comparing persons with MS to healthy controls with regard to having been breastfed during the first 2 years of life were eligible for inclusion. A random effects meta-analysis was calculated to estimate pooled effect sizes using the Mantel-Haenszel method for dichotomous outcomes. The Newcastle-Ottawa Scale was used for quality analysis. Results: 15 studies (13 case-control, 2 cohort) were included of which 12 were rated as high quality. The meta-analysis of crude odds ratios (ORs) yielded a risk estimate of ORcrude = 0.82 (95% confidence interval [CI]: 0.70–0.96) for MS in breastfed versus non-breastfed individuals with substantial heterogeneity (I2 = 68.2%). Using adjusted OR, when available, reduced heterogeneity (I2 = 48.9%) and resulted in an ORadjusted = 0.86 (95% CI: 0.75–0.99). Restricting the analysis to studies with high-quality scores (i.e., ≥6/9 points) resulted in a combined ORcrude of 0.79 (95% CI: 0.66–0.94) and an ORadjusted = 0.83 (95% CI: 0.71–0.98), respectively. Discussion/Conclusion: The meta-analysis showed a small protective effect of having been breastfed on MS risk. This adds to the knowledge that breastfeeding is beneficial for the immunological health of a child. Future studies on the influence of having been breastfed on MS risk should apply a uniform definition of breastfeeding and investigate possible sex-specific aspects.

Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer–specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5–25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06–1.34)]; current versus never smoking [1.37 (1.27–1.47)], high versus low physical activity [0.43 (0.21–0.86)], age ≥30 years versus 0– Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.

Introduction: Monogenic diseases play an important role in critically ill neonates and infants treated in the intensive care unit. This study aimed to determine the diagnostic yield of whole-exome sequencing (WES) for monogenic diseases and identify phenotypes more likely associated with a genetic etiology. Methods: From March 2017 to 2020, a comprehensive diagnostic workup including WES in a single academic center was performed in 61 unrelated, critically ill neonates and infants with an unknown underlying disease within the first year of life. We conducted 59 trio-WES, 1 duo-WES, and 1 single-WES analyses. Symptoms were classified according to the Human Phenotype Ontology. Results: The overall molecular genetic diagnostic rate within our cohort was 46% (28/61) and 50% (15/30) in the subgroup of preterm neonates. Identifying the genetic cause of disease facilitates individualized management in the majority of patients. A positive or negative predictive power of specific clinical features for a genetic diagnosis could not be observed. Conclusion: WES is a powerful noninvasive diagnostic tool in critically ill neonates and infants with a high diagnostic rate. We recommend initiating WES as early as possible due to the impact on management and family counseling. Recommendations regarding the clinical utility of WES in critically ill neonates and infants should not be based on the phenotype alone. Here, we present a clinical workflow for the application of WES for critically ill neonates and infants in an interdisciplinary setting.

Background The number of elderly cancer survivors is growing because of increasing survival rates. A high comorbidity burden in the elderly can affect their quality of life and survival. The aim of this study was to examine whether breast cancer survivors and population-based controls have a different comorbidity burden after long-term follow-up. Methods This study used data from a German breast cancer case-control study, which initially comprised 3813 breast cancer cases aged 50 to 74 years who were diagnosed between 2002 and 2005 and 7341 population-based controls. Participants were followed up in 2014/2016. A modified Charlson Comorbidity Index (mCCI) was calculated to quantify severe comorbidities. Negative binomial regression was performed to estimate rate ratios (RRs) with 95% confidence intervals (CIs) for the association between case-control status and mCCI (dependent variable) for the baseline population and for those who participated at follow-up, with adjustments made for relevant lifestyle factors. Results In total, 1925 cases and 3674 controls participated in the follow-up 12 years after recruitment. In the baseline population 35% had at least 1 comorbid condition.In long-term survivors this proportion was 52%. No difference was found in the mCCI between breast cancer cases and controls at baseline (RR, 1.05; 95% CI, 0.98-1.11) or between long-term survivors of the 2 groups at baseline (RR, 1.07; 95% CI, 0.97-1.18) or at follow-up (RR, 1.00; 95% CI, 0.91-1.10). Conclusions The comorbidity burden of long-term breast cancer survivors and controls increased over time; however, it remained similar in both groups after 12 years of follow-up.

Smoking cessation after a cancer diagnosis can reduce adverse cancer treatment outcomes. Whether a breast cancer diagnosis, a cancer commonly seen as unrelated to smoking cigarettes, motivates changes in smoking behavior is not fully understood. We aimed to compare long-term changes at three follow-up times of cigarette smoking behavior in women with breast cancer and baseline age- and region-matched unaffected women.We used longitudinal data from the population-based case-control study MARIE (Mamma Carcinoma Risk Factor Investigation). Women with breast cancer (N = 3813) and unaffected women (N = 7341) aged 50-74 years were recruited from 2002 to 2005. Analyses on changes in smoking were based on data from those who also completed follow-up 1 in 2009-2012, follow-up 2 in 2014-2016 and follow-up 3 in 2020. Multinomial logistic regression for changes (quitting, stable, or start smoking) adjusted for age, study region, education, comorbidities, living situation, and follow-up time, was applied to examine the associations between breast cancer status and changes in smoking behavior.Women with breast cancer had significantly higher odds than unaffected women of quitting smoking (OR = 1.38, 95 % CI: 1.01-1.89) and lower odds of returning to smoking (OR = 0.29, 95 % CI: 0.09-0.94) at follow-up 1, but were more likely to start or return to smoking at follow-up 2 (OR = 2.11, 95 % CI 1.08-4.15). No significant group differences were found for changes in smoking behavior at follow-up 3.Our findings indicate that short-term changes in smoking behavior can be attributed to a breast cancer diagnosis, but that over time the effect diminishes and changes in smoking no longer differ between breast cancer and breast cancer-free women. To support smoking cessation and to prevent relapse, guidelines to address smoking in cancer care, as well as comprehensive tobacco treatment services, are needed.

More women are surviving after breast cancer due to early detection and modern treatment strategies. Body weight also influences survival. We aimed to characterize associations between postdiagnosis weight change and prognosis in postmenopausal long-term breast cancer survivors. We used data from a prospective population-based patient cohort study (MARIE) conducted in two geographical regions of Germany. Breast cancer patients diagnosed 50 to 74 years of age with an incident invasive breast cancer or in situ tumor were recruited from 2002 to 2005 and followed up until June 2015. Baseline weight was ascertained at an in-person interview at recruitment and follow-up weight was ascertained by telephone interview in 2009. Delayed entry Cox proportional hazards regression was used to assess associations between relative weight change and all-cause mortality, breast cancer mortality, and recurrence-free survival. In total, 2216 patients were included. Compared to weight maintenance (within 5%), weight loss >10% increased risk of all-cause mortality (HR 2.50, 95% CI 1.61, 3.88), breast cancer mortality (HR 3.07, 95% CI 1.69, 5.60) and less so of recurrence-free survival (HR 1.43, 95% CI 0.87, 2.36). Large weight gain of >10% also increased all-cause mortality (HR 1.64, 95% CI 1.02, 2.62) and breast cancer mortality (HR 2.25, 95% CI 1.25, 4.04). Weight maintenance for up to 5 years in long-term breast cancer survivors may help improve survival and prognosis. Postdiagnosis fluctuations in body weight of greater than 10% may lead to increased mortality. Survivors should be recommended to avoid large deviations in body weight from diagnosis onwards to maintain health and prolong life.

HINTERGRUND: In der NAKO Gesundheitsstudie liegen die Daten zu selbstberichteten Krebserkrankungen der ersten Hälfte der Teilnehmenden vor. ZIEL: Beschreibung der Methoden zur Erfassung selbstberichteter Krebserkrankungen und Tumorlokalisationen in der NAKO und Darstellung erster Ergebnisse. MATERIAL UND METHODEN: In einem computergestützten, standardisierten persönlichen Interview wurden 101.787 Teilnehmende (54.526 Frauen, 47.261 Männer) gefragt, ob bei ihnen jemals eine Krebserkrankung (bösartiger Tumor einschließlich in situ) ärztlich diagnostiziert wurde und wie viele Krebserkrankungen sie hatten. Anhand einer Liste wurde die Tumorlokalisation erfragt. Absolute und relative Häufigkeiten von Selbstangaben zu Krebserkrankungen insgesamt und einzelnen Tumorlokalisationen wurden berechnet und mit krebsregisterbasierten Daten verglichen. ERGEBNISSE: Eine ärztlich diagnostizierte Krebserkrankung wurde von 9,4 % der Frauen und 7,0 % der Männer berichtet. Von den Personen, die eine Krebserkrankung berichteten, gaben 88,3 % der Teilnehmenden an, nur eine Krebserkrankung gehabt zu haben. Bei Frauen war die häufigste bösartige Krebserkrankung Brustkrebs, gefolgt von Gebärmutterhalskrebs und malignem Melanom, bei Männern Prostatakrebs, gefolgt von malignem Melanom und Darmkrebs. Beim Vergleich der Krebserkrankungen, die von 45- bis 74-jährigen NAKO-Teilnehmenden in den letzten fünf Jahren berichtet wurden, mit krebsregisterbasierten 5‑Jahres-Prävalenzen wurden für die meisten Tumorlokalisationen in der NAKO niedrigere relative Häufigkeiten beobachtet. Vergleichsweise häufiger traten das maligne Melanom sowie Gebärmutterhalskrebs und Leberkrebs bei Frauen und Harnblasenkrebs und Brustkrebs bei Männern auf. DISKUSSION: Die NAKO ist eine reichhaltige Datenbasis für die zukünftige Untersuchung inzidenter Krebserkrankungen. BACKGROUND: In the German National Cohort (NAKO Gesundheitsstudie), the largest prospective cohort study in Germany, data on self-reported cancer diagnoses are now available for the first half of participants. OBJECTIVES: Description of the methods to assess self-reported cancer diagnoses and type of cancer in the NAKO and presentation of first results. MATERIAL AND METHODS: In a computer-assisted, standardized personal interview, 101,787 participants (54,526 women, 47,261 men) were asked whether they had ever been diagnosed with cancer (malignant tumors including in situ) by a physician and how many cancer diagnoses they had. The type of cancer was classified with a list. Absolute and relative frequencies of self-reported cancer diagnoses and types of cancer were calculated and compared with cancer registry data. RESULTS: A physician-diagnosed cancer was reported by 9.4% of women and 7.0% of men. Of the participants who reported a cancer diagnosis, 88.3% reported to have had only one cancer diagnosis. In women, the most frequent malignancies were breast cancer, cervical cancer, and melanoma. In men, the most frequent malignancies were prostate cancer, melanoma, and colorectal cancer. Comparing the frequencies of cancer diagnoses reported by 45- to 74-year-old NAKO participants within the last five years to cancer registry-based 5‑year prevalences, most types of cancer were less frequent in the NAKO, with the exception of melanoma in men and women, cervical cancer and liver cancer in women, and bladder cancer and breast cancer in men. CONCLUSIONS: The NAKO is a rich data basis for future investigations of incident cancer.

Die korperliche Aktivitat stellt ein komplexes Verhalten dar, dessen valide und reliable Erfassung in gros angelegten populationsbasierten Studien mit besonderen Herausforderungen einhergeht. In der bundesweiten NAKO Gesundheitsstudie liegen zur Halbzeit der Basiserhebung die Daten zur korperlichen Aktivitat fur 100.000 Teilnehmende vor. Beschreibung der Erfassung der korperlichen Aktivitat und Prasentation erster deskriptiver Ergebnisse. Das multimodale Erhebungskonzept bestand aus zwei Fragebogen, dem Questionnaire on Annual Physical Activity Pattern (QUAP) und dem Global Physical Activity Questionnaire (GPAQ), einem computerbasierten Erinnerungsprotokoll der vergangenen 24 h (cpar24) und einer 7‑Tage-Akzelerometrie (Actigraph GT3X/+; Fa. ActiGraph, Pensacola, FL, USA). Fur die einzelnen Erhebungsmodule lagen auswertbare Datensatze in unterschiedlicher Zahl vor (QUAP: n = 16.372; GPAQ: n = 90.900; cpar24: n = 23.989; Akzelerometrie: n = 35.218). Die Analysen der einzelnen Module ergaben unterschiedliche Durchschnittswerte fur die moderate oder intensive korperliche Gesamtaktivitat der Teilnehmenden: Bei Frauen wurden 75–216 min/Tag gemessen, bei Mannern 73–224 min/Tag. Personen der Altersgruppe 20–39 Jahre verbrachten 66–200 min/Tag in moderater oder intensiver korperlicher Gesamtaktivitat, wahrend Personen der Altersgruppe 40–69 Jahre 78–244 min/Tag aufwendeten. Erste modulubergreifende Analysen der korperlichen Aktivitat in der NAKO zeigen den Nutzen komplementar eingesetzter Erhebungsmethoden. Die umfangreichen Daten stellen eine wertvolle Ressource fur die Charakterisierung der Zusammenhange zwischen korperlicher Aktivitat und Krankheitspravention dar, die in der Zukunft erfolgen soll.

HINTERGRUND: Personen mit Migrationshintergrund (PmM) unterscheiden sich als Bevölkerungsgruppe hinsichtlich Morbidität, Mortalität und Inanspruchnahme des Gesundheitssystems meist von der autochthonen Bevölkerung, sie nehmen jedoch seltener an Gesundheitsstudien teil. Die Gruppe der PmM ist sehr heterogen, was in Studien bisher kaum berücksichtigt wird. ZIEL DER ARBEIT: Es werden soziodemografische Charakteristika der PmM in der NAKO Gesundheitsstudie (Alter, Geschlecht, Zeit seit Migration, Bildung) dargestellt. Zudem wird exemplarisch untersucht, ob der Migrationshintergrund mit der Nutzung des Angebots zur Früherkennung von Darmkrebs (Hämoccult-Test) zusammenhängt. METHODEN: Daten der ersten 101.816 Teilnehmenden der NAKO wurden deskriptiv und kartografisch ausgewertet. Die Zuweisung des Migrationshintergrunds erfolgte anhand der Definition des Statistischen Bundesamts und basiert auf Staatsangehörigkeit, Geburtsland, Einreisejahr und Geburtsland der Eltern. ERGEBNISSE: Der Anteil der PmM liegt bei 16,0 %. Die Verteilung über die 18 Studienzentren variiert zwischen 6 % (Neubrandenburg) und 33 % (Düsseldorf). Mit 153 Herkunftsländern sind in der NAKO die meisten Länder vertreten. Bei allen Variablen zeigen sich deutliche Unterschiede zwischen den verschiedenen Herkunftsregionen. Am Hämoccult-Test nehmen türkeistämmige Personen (OR = 0,67) und Aussiedler aus der ehemaligen Sowjetunion (OR = 0,60) seltener teil. PmM, die in Deutschland geboren sind, unterscheiden sich diesbezüglich nicht von der autochthonen Bevölkerung (OR = 0,99). DISKUSSION: PmM in der NAKO sind eine sehr heterogene Gruppe. Jedoch lassen sich aufgrund der Stichprobengröße einzelne Untergruppen der PmM hinsichtlich ihrer Herkunftsregion separat untersuchen. BACKGROUND: Persons with a migration background (PmM) as a population group usually differ from the autochthonous population in terms of morbidity, mortality, and use of the health care system, but they participate less frequently in health studies. The PmM group is very heterogeneous, which has hardly been taken into account in studies so far. OBJEKTIVES: Sociodemographic characteristics of PmM in the NAKO health study (age, sex, time since migration, education) are presented. In addition, it is examined through an example whether migration background is related to the use of cancer screening for colorectal cancer (hemoccult test). METHODS: Data of the first 101,816 persons of the NAKO were analyzed descriptively and cartographically. The migration background was assigned on the basis of the definition of the Federal Statistical Office, based on nationality, country of birth, year of entry, and country of birth of the parents. RESULTS: Overall, the PmM proportion is 16.0%. The distribution across the 18 study centers varies considerably between 6% (Neubrandenburg) and 33% (Düsseldorf). With 153 countries of origin, most countries are represented in the NAKO. All variables show clear differences between the different regions of origin. In the hemoccult test, persons of Turkish origin (OR = 0.67) and resettlers (OR = 0.60) have a lower participation rate. PmM born in Germany do not differ in this respect from the autochthonous population (OR = 0.99). CONCLUSION: PmM in the NAKO are a very heterogeneous group. However, due to the sample size, individual subgroups of migrants can be studied separately with respect to region of origin.

(1) Background: Global incidence of type 1 diabetes (T1D) is rising and nearly half occurred in adults. However, it is unclear if certain early-life childhood T1D risk factors were also associated with adult-onset T1D. This study aimed to assess associations between birth order, delivery mode or daycare attendance and type 1 diabetes (T1D) risk in a population-based cohort and whether these were similar for childhood- and adult-onset T1D (cut-off age 15); (2) Methods: Data were obtained from the German National Cohort (NAKO Gesundheitsstudie) baseline assessment. Self-reported diabetes was classified as T1D if: diagnosis age ≤ 40 years and has been receiving insulin treatment since less than one year after diagnosis. Cox regression was applied for T1D risk analysis; (3) Results: Analyses included 101,411 participants (100 childhood- and 271 adult-onset T1D cases). Compared to “only-children”, HRs for second- or later-born individuals were 0.70 (95% CI = 0.50–0.96) and 0.65 (95% CI = 0.45–0.94), respectively, regardless of parental diabetes, migration background, birth year and perinatal factors. In further analyses, higher birth order reduced T1D risk in children and adults born in recent decades. Caesarean section and daycare attendance showed no clear associations with T1D risk; (4) Conclusions: Birth order should be considered in both children and adults’ T1D risk assessment for early detection.

BACKGROUND: Numerous studies have reported an increase in mental disorders during the COVID-19 pandemic, but the exact reasons for this development are not well understood. In this study we investigate whether pandemic-related occupational and financial changes (e.g., reduced working hours, working from home, financial losses) were associated with increased symptoms of depression and anxiety compared with the situation before the pandemic. METHODS: We analyzed data from the German National Cohort (NAKO) Study. Between May and November 2020, 161 849 study participants answered questions on their mental state and social circumstances. Their responses were compared with data from the baseline survey before the pandemic (2014–2019). Linear fixed-effects models were used to determine whether individual changes in the severity of symptoms of depression (PHQ-9) or anxiety (GAD-7) were associated with occupational/ financial changes (controlling for various covariates). RESULTS: The prevalence of moderate or severe symptoms of depression and anxiety increased by 2.4% and 1.5%, respectively, during the COVID-19 pandemic compared with the preceding years. The mean severity of the symptoms rose slightly. A pronounced increase in symptoms was observed among those who became unemployed during the pandemic (+ 1.16 points on the depression scale, 95% confidence interval [0.91; 1.41], range 0–27). Increases were also seen for reduced working hours with no short-time allowance, increased working hours, working from home, insecurity regarding employment, and financial strain. The deterioration in mental health was largely statistically explained by the occupational and financial changes investigated in the model. CONCLUSION: Depressive symptoms and anxiety disorders increased slightly in the study population during the first year of the COVID-19 pandemic. Occupational and financial difficulties were an essential contributory factor. These strains should be taken into account both in the care of individual patients and in the planning of targeted prevention measures.

Experimental studies suggest that bone fractures result in the release of cytokines and cells that might promote metastasis. Obtaining observational data on bone fractures after breast cancer diagnoses related to distant breast cancer recurrence could help to provide first epidemiological evidence for a metastasis-promoting effect of bone fractures. We used data from the largest German statutory health insurance fund (Techniker Krankenkasse, Hamburg, Germany) in a population-based cohort study of breast cancer patients with ICD-10 C50 codes documented between January 2015 and November 2019. The risk of metastasis overall, regional, distant non-bone or bone metastasis related to a fracture was modeled by an adjusted discrete time-to-event analysis with time-dependent exposure. Of 154,000 breast cancer patients, 84,300 fulfilled the inclusion criteria and had a follow-up time of more than half a year. During follow-up, fractures were diagnosed in 13,579 (16.1%) patients. Metastases occurred in 7047 (8.4%) patients; thereof 1544 had affected regional lymph nodes only and 5503 distant metastases. Fractures demonstrated a statistically significant association with subsequent metastasis overall (adjusted HR 1.12, 95% CI 1.04, 1.20). The highest risk for metastasis was observed in patients with subsequent bone metastasis (adjusted HR 1.18, 95% CI 1.05, 1.34), followed by distant non-bone metastasis (adjusted HR 1.16, 95% CI 1.07, 1.26) and lymph node metastasis (adjusted HR 1.08, 95% CI 0.97, 1.21).

Simple Summary Breast cancer survivors often experience long-term side-effects of the disease and its treatment that negatively impact their quality of life. However, to date only few long-term studies on breast cancer survivor’s quality of life exist and it is unclear whether or not breast cancer survivors experience a worse quality of life than women without breast cancer. We therefore investigated breast cancer survivor’s quality of life before diagnosis, during active treatment as well as 5 and 10 years after diagnosis and compared it to the quality of life in women without breast cancer. We found that breast cancer survivor’s quality of life over all ages improved in the first 5 years and then started to deteriorate. After 10 years it was comparable to women without breast cancer. Yet, we showed that survivors of different ages experience differences in health related quality of life over time. Most importantly, we showed that 10 years after diagnosis younger patients reported a worse quality of life than women of the same age that never had breast cancer. These findings are important when trying to optimize long-term care of breast cancer survivors. Abstract Background: Breast cancer (BC) survivors often suffer from late and long-term residual symptoms of the disease and its treatment. To date, long-term health-related quality of life (HRQoL) in breast cancer survivors has been seldom investigated and rarely compared to unaffected women (controls). Aim: This study aimed to investigate HRQoL over time using patient-reported status before diagnosis, during treatment, 1 year post-surgery, approx. 5 years and ≥10 years post-diagnosis. We also compared survivors’ HRQoL with controls’ still alive 10 years after recruitment. Methods: Data from the German population-based Mamma Carcinoma Risk Factor Investigation (MARIE) cohort of 1123 BC patients aged 50–74 years at diagnosis (2002–2005) and of 3453 matched controls were used for analysis. HRQoL was assessed with the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) questionnaire. All analyses were conducted for all ages as well as stratified according to three age groups (≤58 years, 59–64 years, ≥64 years). Differences in survivors’ general HRQoL before, during, and after therapy were investigated using a t-test/Wilcoxon signed-rank test. Changes in the HRQoL of survivors stratified by age from FU1 to FU2 were assessed via repeated analysis of variance. The HRQoL of survivors compared to the controls at FU2 was analyzed using an analysis of variance. Results: Over all ages, the general HRQoL in patients improved in the first 5 years post-diagnosis. In the subsequent years, HRQoL slightly deteriorated but was comparable to that of the controls. Younger survivors mostly improved their HRQoL from the 5 to 10-year follow-up but remained negatively affected for most functioning and symptom scales compared to controls. In older survivors, HRQoL hardly changed over time and detriments were less pronounced compared to controls, except for insomnia. Conclusions: Restrictions of HRQoL persist for more than 10 years and are most prominent among younger survivors. Researchers and clinicians should be aware of such potential deteriorations and age-dependent differences in order to optimize/adapt long-term cancer survivor care.

Neurological symptoms are frequent and often a leading feature of childhood-onset mitochondrial disorders (MD) but the exact incidence of MD in unselected neuropediatric patients is unknown. Their early detection is desirable due to a potentially rapid clinical decline and the availability of management options. In 491 children with neurological symptoms, a comprehensive diagnostic work-up including exome sequencing was performed. The success rate in terms of a molecular genetic diagnosis within our cohort was 51%. Disease-causing variants in a mitochondria-associated gene were detected in 12% of solved cases. In order to facilitate the clinical identification of MDs within neuropediatric cohorts, we have created an easy-to-use bedside-tool, the MDC-NP. In our cohort, the MDC-NP predicted disease conditions related to MDs with a sensitivity of 0.83, and a specificity of 0.96.

Recent experimental studies indicate that bone fractures result in the release of cytokines and cells that promote metastasis. Obtaining observational data on bone fractures after breast cancer diagnosis related to distant breast cancer recurrence risk could help determine whether fall prevention strategies can contribute to reduce breast cancer mortality. We used data from the largest German statutory health insurance fund (Techniker Krankenkasse) in a population-based cohort study of breast cancer patients diagnosed between January 2015 and November 2019. ICD-10 codes were documented monthly to quarterly. Fractures diagnosed simultaneous or after the initial breast cancer and metastases diagnosed initially from half a year later on served as exposure and outcome, respectively. The risk of regional, distant non-bone or bone metastasis related to a fracture was modelled by adjusted conditional logistic regression analysis. Of 154,000 breast cancer patients, 82,039 had a follow-up time of more than half a year. During follow-up, fractures were diagnosed in 11,900 (14.5%) patients and regional or distant metastases occurred in 7,011 (8.5%). The risk for a metastasis was reduced in patients, who had a fracture (OR 0.57, 95% CI 0.53, 0.62) compared to patients without, particularly for lymph node metastasis and moderately less pronounced in bone-metastasis (OR 0.69, 95% CI 0.61, 0.79). In view of the positive effects of sports on health of cancer survivors, the present results will decrease the anxiety of breast cancer patients that risking bone fractures might have a negative impact on their disease-specific outcome.

It is unclear whether a breast cancer diagnosis affects health behaviour changes that occur with ageing. We aimed to compare long-term changes of alcohol consumption, body weight, and physical activity in women with breast cancer and in age-matched unaffected women.We used data from 1,925 women with breast cancer and 3,473 unaffected women aged 50-74 years enrolled in the population-based case-control study MARIE (Mamma Carcinoma Risk Factor Investigation) in 2002-2005, who also completed the follow-up in 2014-2016. Multinomial logistic regression was applied to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations between breast cancer status and categories of change in alcohol consumption, weight and physical activity.After 11.6 years of follow-up, breast cancer survivors had significantly lower odds than unaffected women of increasing alcohol consumption from ≤10 to10 g/day (adjusted OR 0.48, 95 % CI 0.35-0.65), but were more likely to experience a major weight change of ≥10 % compared to having stable weight (±5 %) (OR for increase and decrease 1.32, 95 % CI 1.03-1.70 and 1.36, 95 % CI 1.05-1.77, resp.) and to decrease transport physical activity to below 2.5 h/week compared to maintaining the activity level (OR 1.61, 95 % CI 1.26-2.04). No significant group difference was found for changes in recreational physical activity.Our data indicate that some long-term health behaviour changes can be attributed to a breast cancer diagnosis rather than ageing, suggesting that long-term medical care of breast cancer survivors could pay greater attention to weight control and sufficient physical activity.

In epidemiologic studies, standardised measurement of socio-demographic and employment-related factors is becoming increasingly important, as variables such as gender, age, education or employment status are factors influencing health and disease risks.The article gives an overview of the scientific background and assessment of socio-demographic factors in the German National Cohort Study. In addition, the distribution of individual characteristics in the cohort as well as relationships with health-related measures are presented by way of example.The analysis is based on the data of the first half of the baseline survey (n = 101,724). On this basis, we present the distribution of key socio-demographic characteristics and analyse relationships with exemplary selected health indicators (body mass index, self-reported health) to assess the validity of socio-demographic data measurements.On average, study participants were 52.0 years old (SD = 12.4). Of the participants, 53.6% were women, 54.3% had high education, 60.1% were married and 72% were employed while 3.4% were unemployed. Well-established correlations between socio-demographic factors and health could be reproduced with the German National Cohort data. For example, low education, old age and unemployment were associated with an increased prevalence of obesity and poor self-reported health.The German National Cohort provides a comprehensive measurement of socio-demographic characteristics. Combined with a wide range of health data and the longitudinal measurements available in the future, this opens up new opportunities for health science and social epidemiological research in Germany.

BACKGROUND: Persons with a migration background (PmM) as a population group usually differ from the autochthonous population in terms of morbidity, mortality, and use of the health care system, but they participate less frequently in health studies. The PmM group is very heterogeneous, which has hardly been taken into account in studies so far. OBJECTIVES: Sociodemographic characteristics of PmM in the NAKO health study (age, sex, time since migration, education) are presented. In addition, it is examined through an example whether migration background is related to the use of cancer screening for colorectal cancer (hemoccult test). METHODS: Data of the first 101,816 persons of the NAKO were analyzed descriptively and cartographically. The migration background was assigned on the basis of the definition of the Federal Statistical Office, based on nationality, country of birth, year of entry, and country of birth of the parents. RESULTS: Overall, the PmM proportion is 16.0%. The distribution across the 18 study centers varies considerably between 6% (Neubrandenburg) and 33% (Düsseldorf). With 153 countries of origin, most countries are represented in the NAKO. All variables show clear differences between the different regions of origin. In the hemoccult test, persons of Turkish origin (OR = 0.67) and resettlers (OR = 0.60) have a lower participation rate. PmM born in Germany do not differ in this respect from the autochthonous population (OR = 0.99). CONCLUSION: PmM in the NAKO are a very heterogeneous group. However, due to the sample size, individual subgroups of migrants can be studied separately with respect to region of origin.

High levels of adiposity in the population have a major impact on various diseases, but previous epidemiologic studies have largely been restricted to simple anthropometric measures such as the body mass index (BMI), an imperfect predictor of disease risk. There is a critical need for the use of improved measures of relative weight and body composition in large-scale, population-based research.The current article presents initial descriptive results of body composition and fat distribution based on the midterm baseline dataset of the German National Cohort, which included 101,817 participants who were examined in 18 study centers in Germany between March 2014 and March 2017. The anthropometric measures encompassed body weight, height, waist and hip circumference, bioelectrical impedance analysis (BIA), sonography of abdominal adipose tissue, 3D-body scanning, and magnetic resonance imaging.BMI analyses showed that 46.2% of men and 29.7% of women were overweight and 23.5% of men and 21.2% of women were obese. On average, women in almost all age groups demonstrated more subcutaneous adipose tissue layer thickness than men. The mean values of visceral adipose tissue layer thickness, on the other hand, were higher among men than among women in all age groups and increased continuously across age groups in both sexes.The comprehensive assessment of body composition and fat distribution provides novel future opportunities for detailed epidemiologic analyses of overweight and adiposity in relation to the development of chronic diseases.

HINTERGRUND: Muskuloskelettale Symptome und Erkrankungen sind in der Bevölkerung sehr weit verbreitet und verursachen hohe Kosten in Gesundheitswesen und Volkswirtschaft. ZIEL DER ARBEIT: Die Häufigkeit muskuloskelettaler Symptome und Erkrankungen aus den Bereichen Rückenschmerzen, Osteoporose, Arthrose und Arthritis wurde auf Basis von Daten der bevölkerungsbasierten NAKO Gesundheitsstudie beschrieben. MATERIAL UND METHODEN: Die Daten wurden in der ersten Hälfte der NAKO-Basiserhebung von März 2014 bis März 2017 bei Erwachsenen im Alter von 20–75 Jahren erhoben. In die Analysen gingen Daten von 101.779 Interviewteilnehmenden sowie von 9370 Teilnehmenden aus zwei klinischen Untersuchungen ein. Mittels der klinischen Handuntersuchung wurden tastbar geschwollene Gelenke sowie auf Druck schmerzhafte Gelenke identifiziert. Die Winkelstuhluntersuchung lieferte Daten zu Ruheschmerzen am Knie- und Hüftgelenk. Häufigkeiten wurden auf die deutsche Standardbevölkerung 2011 gewichtet. ERGEBNISSE: In den Selbstberichten der Teilnehmenden im Interview wurden am häufigsten jemals diagnostizierte andauernde Rückenschmerzen (22,5 %) und Arthrosen (20,6 %) angegeben, seltener Osteoporose (2,9 %) und rheumatoide Arthritis (1,9 %). In der Handuntersuchung wurden bei 6,0 % Schmerzen an mindestens einem Fingergelenk festgestellt. Laut Winkelstuhluntersuchung waren 8,2 % von einem Ruheschmerz in mindestens einem Knie betroffen sowie 5,1 % an der Hüfte. Frauen berichteten insgesamt häufiger muskuloskelettale Erkrankungen und Symptome als Männer, der Anteil Betroffener nahm mit dem Alter deutlich zu. DISKUSSION: Die Ergebnisse belegen die große Verbreitung vieler muskuloskelettaler Erkrankungen. Die berichtete Beschwerdelast ist mit Ergebnissen aus früheren bevölkerungsbezogenen Erhebungen vergleichbar. BACKGROUND: Musculoskeletal diseases and symptoms are very common in the general population. They lead to high healthcare costs and pose a significant burden to the national economy. OBJECTIVES: Based on data from the population-based German National Cohort (GNC), frequencies of musculoskeletal symptoms and diseases are reported, including back pain, osteoporosis, osteoarthritis, and arthritis. MATERIAL AND METHODS: Data were collected from March 2014 to March 2017 in adults aged 20–75 years during the first half of the baseline survey of the GNC. The sample comprised 101,779 interviewed subjects, including 9370 subjects who underwent clinical musculoskeletal examinations. The interview included questions about specific musculoskeletal disorders. A clinical examination of the hand provided information about palpable swollen joints and pressure-sensitive joints. Resting pain of the knees and hips was also assessed by a clinical examination. Frequencies were standardized to the German standard population of the year 2011. RESULTS: Having ever been diagnosed with recurrent back pain (22.5%) or osteoarthritis (20.6%) were the most common complaints reported in the interview; osteoporosis (2.9%) and rheumatoid arthritis (1.9%) were stated more seldom. According to the hand examination, 6.0% of all participants experienced pain in at least one finger joint. Resting pain was present in at least one knee among 8.2% and in at least one hip among 5.1% of the participants as assessed during the clinical examination. Women were more likely to report musculoskeletal disorders and symptoms than men. The proportion of adults affected by musculoskeletal diseases increased strongly with age. CONCLUSION: Musculoskeletal disorders and symptoms occur frequently. The burden of complaints and diagnoses is comparable to previous population-based surveys.

Übergewicht und Adipositas sind bedeutende Risikofaktoren für verschiedene Erkrankungen. Als Maß zu ihrer Bestimmung wurde in früheren Studien meist nur der Body-Mass-Index (BMI) verwendet. Der BMI ist allerdings ein Marker, der den Einfluss auf das Krankheitsrisiko nur unzureichend erfasst. In groß angelegten, bevölkerungsbasierten Studien besteht daher ein vordringlicher Bedarf, verbesserte Messmethoden der Körperzusammensetzung und -fettverteilung einzusetzen. Der vorliegende Beitrag stellt die in der NAKO (Nationale Kohorte) Gesundheitsstudie eingesetzten Messverfahren zur Beschreibung von Körperzusammensetzung und -fettverteilung und die ersten deskriptiven Ergebnisse vor. Diese beziehen sich auf die Daten zur Halbzeit der Basiserhebung, welche 101.817 Teilnehmende einschließt, die in 18 Studienzentren in Deutschland zwischen März 2014 und März 2017 untersucht worden sind. Die anthropometrischen Messungen umfassten Körpergewicht, Körpergröße und -umfänge, bioelektrische Impedanzanalyse (BIA), Sonographie des Abdominalfettes, 3‑D-Bodyscanner und Magnetresonanztomographie. Die Analyse des BMI zeigte, dass 46,2 % der Männer sowie 29,7 % der Frauen übergewichtig und 23,5 % der Männer und 21,2 % der Frauen adipös waren. Frauen wiesen im Mittel in fast allen Altersgruppen eine höhere Schichtdicke an subkutanem Fettgewebe auf als Männer. Die mittlere Schichtdicke des viszeralen Fettgewebes lag hingegen bei den Männern in allen Altersgruppen über den Werten der Frauen und stieg bei beiden Geschlechtern über die Altersgruppen kontinuierlich an. Die umfassenden Daten über die Körperfettverteilung und -zusammensetzung ermöglichen es zukünftig, den Einfluss von Übergewicht und Adipositas auf die Entstehung von chronischen Erkrankungen im Detail zu analysieren. High levels of adiposity in the population have a major impact on various diseases, but previous epidemiologic studies have largely been restricted to simple anthropometric measures such as the body mass index (BMI), an imperfect predictor of disease risk. There is a critical need for the use of improved measures of relative weight and body composition in large-scale, population-based research. The current article presents initial descriptive results of body composition and fat distribution based on the midterm baseline dataset of the German National Cohort, which included 101,817 participants who were examined in 18 study centers in Germany between March 2014 and March 2017. The anthropometric measures encompassed body weight, height, waist and hip circumference, bioelectrical impedance analysis (BIA), sonography of abdominal adipose tissue, 3D-body scanning, and magnetic resonance imaging. BMI analyses showed that 46.2% of men and 29.7% of women were overweight and 23.5% of men and 21.2% of women were obese. On average, women in almost all age groups demonstrated more subcutaneous adipose tissue layer thickness than men. The mean values of visceral adipose tissue layer thickness, on the other hand, were higher among men than among women in all age groups and increased continuously across age groups in both sexes. The comprehensive assessment of body composition and fat distribution provides novel future opportunities for detailed epidemiologic analyses of overweight and adiposity in relation to the development of chronic diseases.

We describe a novel dietary assessment strategy to estimate usual food intake in the ongoing large-scale multi-center German National Cohort (GNC). The dietary assessment is based on three 24 h food lists (24h-FL) and a food frequency questionnaire (FFQ) enriched by information from the representative German National Nutrition Survey II (NVS II). The novelty of this dietary assessment strategy is based on separating the probability of food intake from daily consumption amounts. The probability of consumption is estimated from 24h-FLs used in the GNC. To estimate daily consumption amounts, the already collected data of the NVS II are used. The 24h-FL simplifies the question on food consumption for all foods asked to consumption or not and so the questionnaire can be completed in about 10 minutes, reducing the burden on study participants. As proof of concept, we applied the assessment strategy to pretest data collected in 2012 to 2013 to assess the feasibility of the instruments. In brief, the novel dietary assessment strategy comprises three steps. First, the individuals’ consumption probability is estimated by three 24h-FLs and one FFQ applying a logistic linear mixed model adjusted for characteristics of the participants. Second, person-specific daily consumption amounts are estimated from the NVS II applying a linear mixed model taking the characteristics of the participants into account. Third, usual food intake is estimated by the consumption probability multiplied by person-specific daily amounts. Usual intake of 41 food groups in 318 men and 377 women were estimated. Of those participants who completed the first 24h-FL, 84.4, and 68.5% completed the second and third 24h-FL, respectively. No associations were observed between probability to participate and lifestyle factors. The estimated usual food intake distributions were in a plausible range as shown by comparing the estimated energy intake to the energy needs approximated by estimated total energy expenditure. Total energy was estimated to be 2,707 kcal/day for men and 2,103 kcal/day for women. With a few exceptions, the estimated food-based consumption probabilities did not differ considerably between men and women. The differences in energy intake between men and women were mainly due to their differences in the estimated person-specific daily amounts. As a conclusion, plausible but not validated values for usual food intake were derived in the pretest study, so that the combination of three repeated 24h-FLs, an FFQ and person-specific daily amounts from an external source is a feasible strategy for dietary assessment.