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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.

Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values-8 as genome-wide significant, and p-values-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants.Results: None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values5. The strongest evidence was found for rs4674019 (p-value=2.27x10-7), which showed genome-wide significant interaction (p-value=3.8x10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. Conclusions: In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association.

Background The potential benefit of additional breast cancer screening examinations in moderate risk patients (patients with a history of breast cancer in one or two family members) remains unclear. Methods A large population-based case–control study on breast cancer in postmenopausal women in Germany recruited 2002–2005 (3813 cases and 7341 age-matched controls) was used to assess the association of family history with breast cancer risk. Analysis of family history, participation in screening procedures, and tumor size regarding prognosis in patients was based on follow-up data until 2015. Results A first degree family history of breast cancer was associated with higher breast cancer risk (OR 1.39, p 10 mammograms (MG) (42.7% vs. 24.9%, p, Highlights • Large case-control study with data about family history of breast cancer of 3813 cases and 7341controls and follow-up data. • Breast cancer patients with a first degree family history of breast cancer had a higher number of performed mammograms. • Breast cancer patients with first degree family history of breast cancer also had a higher rate of imaging-detected tumors. • Patients with a positive family history of breast cancer were more likely to have a smaller tumor size at diagnosis. • Imaging-assisted tumor detection was associated with better overall survival.

Highlights • SARS-CoV-2 prevalence in German hospitals less than feared. • Strict hygiene protocols can reduce transmission rates in hospitals. • Longitudinal in-hospital prevalence of SARS-CoV-2 comparable to the general public., Objectives SARS-CoV-2 causing the pulmonary disease COVID-19 has challenged healthcare facilities worldwide. The sustainability of healthcare systems is largely reliant on the health status of their health care workers (HCW). This study was aimed at the detection of SARS-CoV-2 virus and specific antibodies among HCW in a German hospital, as a model system for the potential spread of the pandemic. Methods Between March and June 2020, we performed this study using a combination of RT-PCR test for the detection of SARS-CoV-2 RNA, and ELISA to detect the presence of anti-SARS-CoV-2 immunglobulin G (IgG) antibodies among HCW in a German hospital by repetitive oropharyngeal swabs (OPS) and blood samples. Results A total of 871/1081 employees participated in this prospective longitudinal study. During the study period of 9 weeks, 5329 OPS and 2136 blood samples were analyzed. In three participants (0.34%) SARS-CoV-2 RNA was detected. Anti-SARS-CoV-2-IgG antibodies were detected in 38 (4.36%) participants. Conclusion Our study reports low prevalence of COVID-19 in HCW, which may reflect the effectiveness of hygiene protocols. It might, however, indicate a low prevalence of SARS CoV-2 in hospital employees. Our study protocol may serve as a thought-provoking example for future pandemic containment protocols in hospitals.

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.

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.

Background: Topical corticosteroids (TS) have become standard therapy for eosinophilic esophagitis (EoE). However, a variety of drug formulations have been used for which results of histological and clinical responses may be different. We aimed at determining the short-term histologic efficacy of TS for EoE based on randomized placebo-controlled trials and to review clinical response. Methods: We searched MEDLINE, ISI Web of Science, and clinicaltrials.gov for randomized controlled trials (RCTs) on TS versus placebo for active EoE published until June 2019. Treatment effects were calculated as risk ratios (RRs) comparing histologic remission between groups. Results: Nine RCTs (6 budesonide and 3 fluticasone) involving a total of 483 participants were included. A substantial overall effect of TS on acute histologic remission (RR 12.5, 95% confidence interval 6.0–25.9) was found despite varying definitions of histologic response. Indirect comparisons between drug and formulation types showed a trend for a better histologic efficacy of budesonide (RR 13.5 vs. 10.4 fluticasone) and for the orodispersible tablet (RR 46.2 vs. 11.5 suspension, and 10.4 nebulized formula/spray), but only based on small patient numbers. Scores used for clinical response assessment were different between studies, and short-term clinical results were less impressive: significant differences favoring TS were found in 4/9 RCTs (4/6 budesonide, 0/3 fluticasone). Conclusions: TS are effective for short-term induction of histological remission in EoE with less impressive clinical response rates. The mode of drug delivery to the esophagus may be a relevant factor for the degree of histologic remission. Further trials should use uniform assessment criteria and long-term patient-centered outcomes.

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.

Objective: A multigenetic pro-inflammatory profile may increase stroke risk. We investigated whether a higher number of pro-inflammatory genetic variants are associated with ischaemic stroke risk and whether other risk factors further elevate this risk. Methods: In a case-control study with 470 ischaemic stroke patients (cases) and 807 population controls, we investigated 23 haplotypes or alleles in 16 inflammatory genes (interleukin [IL]1A, IL1B, IL1 receptor antagonist, IL6, IL6 receptor, IL10, tumour necrosis factor-a; C-C motif chemokine ligand 2, C-C motif chemokine receptor 5, C-reactive protein (CRP), intercellular adhesion molecule 1, transforming growth factor β1, E-Selectin, selenoprotein S, cluster determinant 14, histone deacetylase 9 [HDAC9]). We constructed an extended gene score (EGS) as the sum of all individual risk alleles and analysed its effect on stroke, just as its association and interaction with cardiovascular risk factors and infectious scores (IgG antibodies against 5 respectively IgA antibodies against 4 microbial antigens). Results: Cases were less likely to carry the minor allele of IL10 rs1800872 and more likely to carry the HDAC9 allele rs11984041 and the pro-inflammatory haplotype of CRP, although the latter was not statistically significant in our study. Overall, cases tended to have more pro-inflammatory alleles and haplotypes than controls (mean ± SD 13.25 ± 2.25 and 13.04 ± 2.41, respectively). However, the EGS only slightly and not significantly increased the risk of stroke (OR 1.04, 95% CI 0.99–1.09). Its effect was neither associated with included risk factors nor with IgA and IgG infectious scores, and we found no significant interaction effects. Conclusion: A more pro-inflammatory genetic profile might increase stroke risk to some extent. This potential effect is most likely independent of established cardiovascular risk factors and the infectious burden of an individual.

BackgroundFollowing a year of development, several vaccines have been approved to contain the global COVID-19 pandemic. Real world comparative data on immune response following vaccination or natural infection are rare.MethodsWe conducted a longitudinal observational study in employees at a secondary care hospital affected by the COVID-19 pandemic. Comparisons were made about the presence of anti-SARS-CoV-2 immunglobulin G (IgG) antibody ratio after natural infection, or vaccination with one or two doses of BioNTech/Pfizer (BNT162b2), or one dose of AstraZenca (Vaxzevria) vaccine.ResultsWe found a 100% humoral response rate in participants after 2 doses of BNT162b2 vaccine. The antibody ratio in participants with one dose BNT162b2 and Vaxzevria did not differ significantly to those with previous PCR-confirmed infection, whereas this was significantly lower in comparison to two doses of BioNTech/Pfizer. We could not identify a correlation with previous comorbidities, obesity or age within this study. Smoking showed a negative effect on the antibody response (p=0.006)ConclusionOur data provide an overview about humoral immune response after natural SARS-CoV-2 infection or following vaccination, and supports the usage of booster vaccinations, especially in patients after a natural SARS-CoV-2 infection.

Retention is important for statistical power and external validity in long-term cohort studies. The aims of our study were to evaluate different retention strategies within a cohort study of adults of Turkish descent in Berlin, Germany, and to compare participants and non-participants. In 2011–2012, a population-based study was conducted among adults of Turkish descent to primarily examine recruitment strategies. 6 years later, the participants were re-contacted and invited to complete a self-report questionnaire regarding their health status, health care utilization, and satisfaction with medical services. The retention strategy comprised letters in both German and Turkish, phone calls, and home visits (by bilingual staff). We calculated the response rate and retention rate, using definitions of the American Association for Public Opinion Research, as well as the relative retention rate for each level of contact. Associations of baseline recruitment strategy, sociodemographic, migration-related and health-related factors with retention were investigated by logistic regression analysis. Of 557 persons contacted, 249 (44.7%) completed the questionnaire. This was 50.1% of those whose contact information was available. The relative retention rate was lowest for phone calls (8.9%) and highest for home visits (18.4%). Participants were more often non-smokers and German citizens than non-participants. For all remaining factors, no association with retention was found. In this study, among adults of Turkish descent, the retention rate increased considerably with every additional level of contact. Implementation of comprehensive retention strategies provided by culturally matched study personnel may lead to higher validity and statistical power in studies on migrant health issues.

Even though several SARS-CoV-2 vaccines have shown high effectiveness in the prevention of COVID-19 in healthy subjects, vaccination response in patients with plasma-cell-related disorders (PCD) remains widely unknown. Here, we report on an analysis describing the serological response after prime-boost SARS-CoV-2 vaccination in PCD patients, as compared to a healthy control group, and on possible influencing factors of serological responses. Blood samples were analyzed for the presence of quantitative anti-SARS-CoV-2 spike RBD Ig. A total of 82 patients were included; 67 received mRNA-, eight vector-based and four heterologous vaccinations. SARS-CoV-2 antibody titers (SP-AbT) were assessed in a mean of 23 days (SD ± 11 days) after the first and in a mean 21 days (SD ± 9) after prime-boost vaccination. A positive SP-AbT was detected in 31.9% of PCD patients after the first vaccination, and in 88.9% (44/49) after prime-boost vaccination, which was significantly less likely than that in the control group (100%, 78/78) (p = 0.008). Furthermore, we have been able to validate our previously suggested threshold of 30 CD19+ B lymphocytes/µL as being predictive for SP-AbT development. Despite anti-CD38 directed therapy, quadruplet treatment, higher age and missing deep remission, which correlated negatively with SP-AbT appearance, SP-AbT formation is possible in a majority of myeloma patients after prime-boost vaccination.

The new coronavirus (COVID-19) pandemic and the resulting response measures have led to severe limitations of people’s exercise possibilities with diminished physical activity (PA) and increased sedentary behavior (SB). Since for migrant groups in Germany, no data is available, this study aimed to investigate factors associated with changes in PA and SB in a sample of Turkish descent. Participants of a prospective cohort study (adults of Turkish descent, living in Berlin, Germany) completed a questionnaire regarding COVID-19 related topics including PA and SB since February 2020. Changes in PA and SB were described, and sociodemographic, migrant-related, and health-related predictors of PA decrease and SB increase were determined using multivariable regression analyses. Of 106 participants, 69% reported a decline of PA, 36% reported an increase in SB. PA decrease and SB increase seemed to be associated with inactivity before the pandemic as well as with the female sex. SB increase appeared to be additionally associated with educational level and BMI. The COVID-19 pandemic and the response measures had persistent detrimental effects on this migrant population. Since sufficient PA before the pandemic had the strongest association with maintaining PA and SB during the crisis, the German government and public health professionals should prioritize PA promotion in this vulnerable group.

Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease. Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

Simple Summary The global impact of the current COVID-19 pandemic has led to the impressively rapid development of multiple anti-SARS-CoV-2 vaccines. However, only few data are available regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with hematological malignancies, and, in particular, plasma cell neoplasia. This ongoing observational study aimed to describe the level of post-vaccination anti-SARS-CoV-2-antibodies depending on multiple clinical factors including B lymphocyte count and current therapy of 82 patients with multiple myeloma and related plasma cell neoplasia, after the first dose of anti-SARS-CoV-2 vaccination. A positive SARS-CoV-2 spike protein antibody titer (SP-AbT) was detected in 23% of assessable patients. SARS-CoV-2 SP-AbT was significantly higher in patients with higher CD19+ B lymphocyte counts and current treatment with anti-CD38-antibodies has led to significantly reduced SP-AbT titers. Based on our results, the majority of myeloma patients respond poorly after receiving the first dose of any anti-SARS-CoV-2 vaccination and need booster vaccination. Abstract Few data are available regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with hematological malignancies, and particular, plasma cell neoplasia. This ongoing single-center study aimed to describe the level of post-vaccination anti-SARS-CoV-2-antibodies depending on B lymphocyte count, current therapy, and remission status of patients with multiple myeloma and related plasma cell dyscrasia, after the first dose of anti-SARS-CoV-2 vaccination. The 82 patients included in this study received SARS-CoV-2 vaccines (including mRNA- and vector-based vaccines) as a routine measure. After the first vaccination, a positive SARS-CoV-2 spike protein antibody titer (SP-AbT) was detected in 23% of assessable patients. SARS-CoV-2 SP-AbT was significantly higher in patients with higher CD19+ B lymphocyte counts. A cut-off value of ≥30 CD19+ B cells/µL was significantly positive correlating with higher SARS-CoV-2 SP-AbT. In contrast, current treatment with anti-CD38-antibodies has led to significantly reduced SP-AbT titers. Furthermore, in multivariable linear regression, higher age and insufficiently controlled disease significantly correlated negatively with SARS-CoV-2 SP-AbT. Conversely, treatment with immunomodulatory drugs did not harm the development of antibody titers. Based on our results, the majority of myeloma patients respond poorly after receiving the first dose of any anti-SARS-CoV-2 vaccination and need booster vaccination.

COVID-19, which is caused by SARS-CoV-2, is an occupational health risk, especially for healthcare employees due to their higher exposure and consequently higher risk of symptomatic and asymptomatic infections. This study was designed to determine the longitudinal seroprevalence of specific immunoglobulin-G (IgG) antibodies in employees in a hospital setting. All employees in a secondary care hospital, including healthcare and non-healthcare workers, were invited to participate in this single-center study. After an initial screening, a 6-month follow-up was carried out, which included serological examination for SARS-CoV-2 IgG antibodies and a questionnaire for self-reported symptoms, self-perception, and thoughts about local and national hygiene and pandemic plans. The seroprevalence of SARS-CoV-2 IgG antibodies was 0.74% among 406 hospital employees (0.75% in healthcare workers, 0.72% in non-healthcare workers), initially recruited in April 2020, in their follow-up blood specimens in October 2020. In this study, 30.54% of the participants reported using the official German coronavirus mobile application and the majority were content with the local and national rules in relation to coronavirus-related restrictions. At the 6-month follow-up, the 0.74% seroprevalence was below the reported seroprevalence of 1.35% in the general German population. The prevalence in healthcare workers in direct patient care compared with that in workers without direct patient contact did not differ significantly. Further follow-up to monitor the seroprevalence in the high-risk healthcare sector during the ongoing global pandemic is essential.

Background Regional deprivation can increase the risk of illness and adversely affect care outcomes. In this study, we investigated for the German state of Rhineland-Palatinate whether spatial-structural disadvantages are associated with an increased frequency of ischemic stroke and with less favorable care outcomes. Methods We compared billing data from DRG statistics (2008-2017) and quality assurance data (2017) for acute ischemic stroke with the German Index of Multiple Deprivation 2010 (GIMD 2010) for the 36 districts (Landkreise) and independent cities (i.e., cities not belonging to a district) in Rhineland-Palatinate using correlation analyses, a Poisson regression analysis, and logistic regression analyses. Results The age-standardized stroke rates (ASR) ranged from 122 to 209 per 100 000 inhabitants, while the GIMD 2010 ranged from 4.6 to 47.5; the two values were positively correlated (Spearman's ρ = 0.47; 95% confidence interval [0.16; 0.85]). In 2017, mechanical thrombectomies were performed more commonly (5.7%) in the first GIMD 2010 quartile of the regional areas (i.e., in the least deprived areas) than in the remaining quartiles (4.2-4.6%). The intravenous thrombolysis rates showed no differences from one GIMD 2010 quartile to another. Severe neurological deficits (National Institutes of Health Stroke Scale ≥ 5) on admission to the hospital were slightly more common in the fourth quartile (i.e., in the most deprived areas), while antiplatelet drugs and statins were somewhat less commonly ordered on discharge in those areas than in the first quartile. Conclusion These findings document a relationship between regional deprivation and the occurrence of acute ischemic stroke. Poorer GIMD 2010 scores were associated with worse care outcomes in a number of variables, but the absolute differences were small.

Resettlers are a large migrant group of more than 2 million people in Germany who migrated mainly from the former Soviet Union to Germany after 1989. We sought to compare the distribution of the major risk factors for cardiovascular disease (CVD) and to investigate the overall genetic differences in a study population which consisted of resettlers and native (autochthone) Germans. This was a joint analysis of two cohort studies which were performed in the region of Augsburg, Bavaria, Germany, with 3363 native Germans and 363 resettlers. Data from questionnaires and physical examinations were used to compare the risk factors for cardiovascular diseases between the resettlers and native Germans. A population-based genome-wide association analysis was performed in order to identify the genetic differences between the two groups. The distribution of the major risk factors for CVD differed between the two groups. The resettlers lead a less active lifestyle. While female resettlers smoked less than their German counterparts, the men showed similar smoking behavior. SNPs from three genes (BTNL2, DGKB, TGFBR3) indicated a difference in the two populations. In other studies, these genes have been shown to be associated with CVD, rheumatoid arthritis and osteoporosis, respectively.

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.

Background Disadvantageous socioeconomic conditions (SEC) in both childhood and adulthood increase the risk of stroke. We investigated whether intergenerational and lifetime social advancement decreases and/or social descent increases stroke risk. Methods In a case-control study with 466 patients with first-ever ischemic stroke and 807 controls randomly selected from the general population, we compared paternal profession to subjects’ professional education in adolescence and their last profession in adulthood. Furthermore, we constructed a socioeconomic risk score for childhood (based on paternal and maternal profession and occupation, familial, living and material conditions), adolescence (based on highest school degree and professional education), and adulthood (based on last profession, periods of unemployment, and marital status), and compared subjects´ positions at different life stages. Odds ratios were derived based on conditional logistic regression conditioning on age and sex only, after adjustment for medical and lifestyle risk factors, and after additional adjustment for socioeconomic risk score values. Results Intergenerational upward mobility between paternal profession and subject’s professional education was associated with lower ischemic stroke risk independent of medical and lifestyle risk factors (odds ratio (OR) 0.58; 95% confidence interval (CI) 0.41–0.81) and after additional adjustment for socioeconomic conditions in all three life stages (OR 0.67; 95% CI 0.45–0.99). Advancement between fathers´ profession and subject’s last profession was associated with reduced odds of stroke after adjustment for risk factors (OR 0.65; 95% CI 0.47–0.89), but not significantly after additional adjustment for SEC (OR 0.77; 95% CI 0.52–1.13). Social descent between adolescence and adulthood indicated by the transition into a more disadvantageous tertile of socioeconomic risk score was associated with increased odds of stroke after adjustment for all risk factor (OR 2.93; 95% CI 1.21–7.13). Analyses by sex revealed mostly similar results in men and women with only few potential differences. Conclusions Our study results indicate that aspects of social downward mobility during adulthood may be associated with increased risk of stroke, whereas intergenerational upward mobility may be linked to a lower stroke risk. If confirmed by future studies, such results may help to focus stroke prevention measures at high risk populations.

In this study, we analyze clustering of infant deaths within families living in a rural part of western Burkina Faso. The study included 9,220 infants, born between 1993 and 2009 in Nouna Health and Demographic Surveillance System (HDSS). A clustering of infant deaths in families was explored by calculating observed versus expected number of infant deaths within families for a given family size. In addition, risk ratios were calculated for infant death depending on the vital status of the previous sibling. We observed 470 infant deaths, yielding an overall infant mortality risk of 51/1,000 births. Clustering of infant deaths within families was observed (P = 0.004). In smaller families, the mortality of firstborns was higher than for the following siblings. The infant mortality risk was higher when the preceding sibling died in infancy (P = 0.03). The study supports the hypothesis of infant death clustering existing within rural families in West Africa. Further studies are needed to shed more light on these findings with the goal to develop effective interventions directed toward the families who already lost a child.

Background Up to now, only few data are available regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with plasma cell neoplasia. This ongoing observational study aimed to describe the level of post-vaccination anti-SARS-CoV-2-antibodies depending on B lymphocyte count, current therapy, and remission status of patients with multiple myeloma (MM) and related plasma cell dyscrasias, after the first dose of anti-SARS-CoV-2 vaccination. Methods In this single-center study, patients aged 18 years and older with a confirmed diagnosis of MM, monoclonal gammopathies of clinical significance (MGCS) or systemic light-chain amyloidosis (AL) who were eligible for Anti-SARS-CoV-2 vaccination according to the International Myeloma Society recommendations were included. Data were collected between January 1st and May 21th, 2021, at the department of oncology and hematology at the University Medical Center Hamburg-Eppendorf, Germany. The primary aim of this study was to evaluate a possible correlation between antibody titers and CD19+ B lymphocyte count and secondary to identify other possible factors influencing immune response. This study is part of the COVIDOUT trial (NCT04779346). Written informed consent was provided by each patient according to local requirements. Results A total of 82 patients were included in this study. The median age was 67.5 years (range 40-85 years). 78 patients had MM, 2 MGCS, and 2 AL. Overall, 63 patients were vaccinated with mRNA-based and 19 with vector-based vaccines, respectively. At the time of vaccination, 69 (84.1%) patients were under current anti-myeloma treatment. In total, 34 (41%) patients received anti-CD38-targeting therapies and 52 (63%) patients received IMiD-based therapies. 57 (69.5%) patients were in deep remissions (very good partial remission or better) at the time of vaccination. Assessment of anti-SARS-CoV-2 spike protein antibody titer (SP-AbT) took place on a median of 25 days after the first vaccination (SD ± 11.8). A positive SP-AbT was detected in 23% (17/74) of assessable patients. A cut-off value of ≥ 30 CD19+ B cells/µl was significantly positively correlating with higher SARS-CoV-2 SP-AbT. Individuals with current anti-CD38-antibody treatment showed lower SP-AbT and the likelihood for positive titer results was significantly lower in patients with current anti-CD38 treatment compared to those without. Treatment with immunomodulatory drugs did not harm the development of antibody titers. Furthermore, in multivariable linear regression, higher age and insufficiently controlled disease (≤ partial remission) were significantly negatively correlated with SARS-CoV-2 SP-AbT. Conclusion Based on our results, the majority of myeloma patients respond poorly after receiving the first dose of any anti-SARS-CoV-2 vaccination. Since both low CD19+ B lymphocyte count and CD38-directed therapy negatively impact vaccination response, booster vaccination seems therefore of utter importance.

The Lufthansa Prevention Study (LUPS) study is a prospective observation of a healthy worker cohort to identify early changes in metabolism leading to the Metabolic Syndrome (MetS) and to analyze their relation to behavioral factors like nutrition, physical activity, psychological status, and to underlying genetic conditions. The LUPS study recruited a sample of 1.962 non-diabetic healthy adults between 25–60 years, employed at a flight base of Lufthansa Technik GmbH in Hamburg, Germany. Baseline assessments included anthropometric measures, blood and urine samples and medical history. Psychosocial variables, dietary habits and life-style risk factors were assessed via self-reported questionnaires.In this report we describe the study design and present baseline parameters including the prevalence of the MetS using different classification criteria. The MetS was present in 20% of male and 12% of female subjects according to the ‘Harmonizing the metabolic syndrome’ definition. The prevalence varies between 2.6% in male and 2.3% in female subjects up to 48% in male and 41% in female subjects according to different classification criteria of MetS.In conclusion, this first cross-sectional view on the LUPS data confirms the expectation that this cohort is rather healthy and thus provides the opportunity to analyze early changes associated with the development of the MetS. The LUPS study is registered as a clinical trial NCT01313156.

Background: Physical activity (PA) is associated with lower risk of stroke. We tested the hypothesis that lack of pre-stroke PA is an independent predictor of poor outcome after first-ever ischemic stroke. Methods: We assessed recent self-reported PA and other potential predictors for loss of functional independence - modified Rankin Scale (mRS) > 2 - one year after first-ever ischemic stroke in 1370 patients registered between 2006 and 2010 in the Ludwigshafen Stroke Study, a population-based stroke registry. Results: After 1 year, 717 (52.3%) of patients lost their independence including 251 patients (18.3%) who had died. In multivariate logistic regression analysis lack of regular PA prior to stroke (Odds Ratio (OR) 1.7, Confidence Interval (CI) 1.1–2.5), independently predicted poor outcome together with higher age (65–74: OR 1.7; CI 1.1–2.8, 75–84 years: OR 3.3; CI 2.1–5.3; ≥85 years OR 14.5; CI 7.4–28.5), female sex (OR 1.5; CI 1.1–2.1), diabetes mellitus (OR 1.8; CI 1.3–2.5), stroke severity (OR 1.2; CI 1.1–1.2), probable atherothrombotic stroke etiology (OR 1.8; CI 1.1–2.8) and high leukocyte count (> 9.000/mm3; OR 1.4; CI 1.0–1.9) at admission. Subclassifying unknown stroke etiology, embolic stroke of unknown source (ESUS; n = 40, OR 2.2; CI 0.9–5.5) tended to be associated with loss of independence. Conclusion: In addition to previously reported factors, lack of PA prior to stroke as potential indicator of worse physical condition, high leukocyte count at admission as indicator of the inflammatory response and probable atherothrombotic stroke etiology might be independent predictors for non-functional independence in first-ever ischemic stroke.

IntroductionCOVID-19, caused by SARS-CoV-2, is an occupational health risk especially for healthcare employees. This study was designed to determine the longitudinal seroprevalence of specific immunglobolin-G (IgG)-antibodies in employees in a hospital setting.MethodsAll employees including healthcare and non-healthcare workers in a secondary care hospital were invited to participate in this single-center study. After an initial screening, a 6 months follow-up was done which included serological examination for SARS-CoV-2-IgG-antibodies and a questionnaire for self-reported symptoms, self-perception and thoughts about the local and national hygiene and pandemic plans.ResultsThe seroprevalence of SARS-CoV-2-IgG-antibodies was 0.74% among 406 hospital employees (95% confidence interval) (0.75% in healthcare workers, 0.72% in non-healthcare workers), initially recruited in April 2020, in their follow-up blood specimen in October 2020.In this study, 30.54% of the participants reported using the official German corona mobile application and the majority were content with the local and national rules in relation to Coronavirus restrictions.DiscussionAt the 6 months follow-up, the 0.74% seroprevalence was below the reported seroprevalence of 1.35% in the general German population. The prevalence in healthcare workers in direct patient care compared with those without direct patient contact did not differ significantly.

Background Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP Results Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E−08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E−07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E−08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E−08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. Conclusions We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.

Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.

Objectives To illustrate the development of the case fatality risk (CFR) for COVID-19 over time using different assumptions for calculating the CFR. Design Observational study. Setting Selected European countries, 28 January to October 29 2020. Participants Laboratory-confirmed COVID-19 cases and deaths due to COVID-19 Main outcome measure case fatality risk (CFR) Results We show that the CFR has considerably decreased over time. This seems to be driven not only by increased testing but also by a reduced CFR among cases older than 60 years. Our data also confirm a significantly higher fatality risk for men than for women. The decline in the CFR is even more pronounced when only cases and deaths occurring in a specified time window are considered. This alternative estimation method has the advantage that early data where the bias due to the incomplete ascertainment of cases was arguably largest do not affect CFR estimates later on. We find similar results for other European countries. Conclusion CFR estimates vary considerably depending on the underlying assumptions concerning their calculation. Reliable CFR estimates should not be based on cumulative numbers from the beginning of the pandemic but rather be based on more recent data only.

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies. ispartof: AMERICAN JOURNAL OF HUMAN GENETICS vol:107 issue:5 pages:837-848 ispartof: location:United States status: published

Background Studies have shown differences regarding prevalence and incidence of chronic diseases among first (own migration experience) compared to second (born in host country) generation migrants. The aim of this study was therefore to investigate the incidence of cardiovascular diseases (CVD) among persons of Turkish descent with and without migration experience living in Berlin, Germany. Methods In 2012-2013, Berliners with a Turkish migration background were recruited, examined, and contacted again 5 years later via postal mail. Incidence of diagnosed CVD (myocardial infarction, stroke, coronary heart disease, heart failure, cardiac arrhythmia, intermittent claudicatio or transient ischaemic attack) was assessed via self-report. Incidence of any CVD is presented as number and percentages. Associations between the incidence of any CVD and having an own migration experience were investigated with uni- and multivariable regression analyses. Results are presented as odds ratios with a 95%-confidence interval (OR, 95%-CI). Results Data of 234 persons of Turkish descent (62.8% women) with a mean age±standard deviation of 44±12.4 years were included in the analyses. Out of these, 79.9% were first generation migrants. First compared to second generation participants differed regarding CVD incidence (any CVD 16.6% vs. 4.3%, respectively; p = 0.03), socio-demographic, and lifestyle factors. After adjusting for these factors, multivariable analysis showed that only BMI (OR 1.12 per BMI point, 95%CI [1.02;1.24], and having a diagnosis of dyslipidemia (OR 4.0, 95%CI [1.45;12.05]), were independently associated with CVD incidence. Conclusions In a cohort study with Berliners of Turkish descent, CVD incidence was associated with increasing BMI and dyslipidemia, but not with own migration experience. Future migration-related public health research needs to focus on the prevention of harmful health behaviours to avoid the progression of overweight/obesity and dyslipidemia. Key messages CVD incidence is higher in persons with migration experience compared to those without. Migration experience is not associated with CVD incidence after adjusting for confounders (e.g. age, BMI).

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.

European countries report large differences in COVID-19 case fatality risk (CFR) and high variation over the year. CFR estimates may both depend on the method used for estimation and of country-specific characteristics. While crude methods simply use cumulative total numbers of cases and deaths, the CFR can be influenced by the demographic characteristics of the cases, case detection rates, time lags between reporting of infections and deaths and infrastructural characteristics, such as healthcare capacities.We used publicly available weekly data from the national health authorities of Germany, Italy, France and Spain on case and death numbers by age group connected to COVID-19 for the year 2020. We propose to use smoothed data of national weekly test rates for case adjustment and investigated the impact of different time lags from case reporting to death on the estimation of the CFR. Finally, we described the association between case fatality and the demand for hospital beds for COVID-19, taking into account national hospital bed capacities.Crude CFR estimates differ considerably between the four study countries with end-of-year values of approximately 1.9%, 3.5%, 2.5% and 2.7% for Germany, Italy, France and Spain, respectively. Age-adjustment reduces the differences considerably, resulting in values of 1.61%, 2.4% and 2% for Germany, Italy and Spain, respectively. France’s age-specific data was restricted to hospitalised cases only and is therefore not comparable in that regard. International crude International CFR time series show smaller differences when adjusting for demographics of the cases or the test rates. Curves adjusted for age structure, testing or time lags show smaller variance over the year and a smaller degree of non-stationarity. The data does not suggest any connection of CFRs to hospital capacities for the four countries under study.

Background Risk diseases and risk factors for stroke include atrial fibrillation, hypertension, diabetes mellitus, smoking, and elevated LDL-cholesterol. Due to modern treatment options, the impact of these risk diseases on subsequent cardiovascular events or death after a first stroke is less clear and needs to be elucidated. We therefore aimed to get insights into the persistence of adverse prognostic effects of these risk diseases and risk factors on subsequent stroke or death events 1 year after the first stroke by using the new weighted all-cause hazard ratio. Methods This study evaluates the 1 year follow-up of 470 first ever stroke cases identified in the area of Ludwigshafen, Germany, with 23 deaths and 34 subsequent stroke events. For this purpose, the recently introduced “weighted all-cause hazard ratio” was used, which allows a weighting of the competing endpoints within a composite endpoint. Moreover, we extended this approach to allow an adjustment for covariates. Results None of these risk factors and risk diseases, most probably being treated after the first stroke, remained to be associated with a subsequent death or stroke [weighted hazard ratios (95% confidence interval) for diabetes mellitus, atrial fibrillation, high cholesterol, hypertension, and smoking are 0.4 (0.2–0.9), 0.8 (0.4–2.2), 1.3 (0.5–2.5), 1.2 (0.3–2.7), 1.6 (0.8–3.6), respectively]. However, when analyzed separately in terms of death and stroke, the risk factors and risk diseases under investigation affect the subsequent event rate to a variable degree. Conclusions Using the new weighted hazard ratio, established risk factors and risk diseases for the occurrence of a first stroke do not remain to be significant predictors for subsequent events like death or recurrent stroke. It has been demonstrated that the new weighted hazard ratio can be used for a more adequate analysis of cardiovascular risk and disease progress. The results have to be confirmed within a larger study with more events.

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.

BACKGROUND: The German National Cohort (NAKO) is an interdisciplinary health study aimed at elucidating causes for common chronic diseases and detecting their preclinical stages. This article provides an overview of design, methods, participation in the examinations, and their quality assurance based on the midterm baseline dataset (MBD) of the recruitment. METHODS: More than 200,000 women and men aged 20–69 years derived from random samples of the German general population were recruited in 18 study centers (2014–2019). The data collection comprised physical examinations, standardized interviews and questionnaires, and the collection of biomedical samples for all participants (level 1). At least 20% of all participants received additional in-depth examinations (level 2), and 30,000 received whole-body magnet resonance imaging (MRI). Additional information will be collected through secondary data sources such as medical registries, health insurances, and pension funds. This overview is based on the MBD, which included 101,839 participants, of whom 11,371 received an MRI. RESULTS: The mean response proportion was 18%. The participation in the examinations was high with most of the modules performed by over 95%. Among MRI participants, 96% completed all 12 MRI sequences. More than 90% of the participants agreed to the use of complementary secondary and registry data. DISCUSSION: Individuals selected for the NAKO were willing to participate in all examinations despite the time-consuming program. The NAKO provides a central resource for population-based epidemiologic research and will contribute to developing innovative strategies for prevention, screening and prediction of chronic diseases. HINTERGRUND: Die NAKO Gesundheitsstudie ist ein bundesweites interdisziplinäres Forschungsvorhaben mit dem Ziel, die Ursachen für chronische Krankheiten und deren vorklinische Stadien zu untersuchen. Der Artikel gibt einen Überblick über das Studiendesign, die Methoden, die Teilnahme an den Untersuchungen und ihre Qualitätssicherung zur Halbzeit der Basiserhebung. METHODEN: Für die Basiserhebung wurden mehr als 200.000 Frauen und Männer im Alter von 20–69 Jahren aus Zufallsstichproben der Allgemeinbevölkerung in 18 Studienzentren rekrutiert (2014–2019). Die Basiserhebung beinhaltet Untersuchungen, Befragungen und Biomaterialien für alle Teilnehmerinnen und Teilnehmer (Level 1), ein erweitertes Programm für mindestens 20 % (Level 2) und eine Magnetresonanztomografie (MRT) für 30.000 Teilnehmerinnen und Teilnehmer. Sekundär- und Registerdaten werden über Krankheitsregister, Kranken- und Rentenversicherungen erhoben. Die Auswertung bezieht die Datenbasis zur Halbzeit der Basiserhebung mit 101.839 Teilnehmerinnen und Teilnehmern ein, davon 11.371 mit einer MRT-Untersuchung. ERGEBNISSE: Die mittlere Responsequote zur Halbzeit betrug insgesamt 18 %. Die Teilnahme an den Untersuchungen lag überwiegend bei mehr als 95 %. Bei 96 % der MRT-Teilnehmerinnen und Teilnehmer konnten alle 12 MRT-Sequenzen vollständig durchgeführt werden. Der Erschließung und wissenschaftlichen Nutzung ergänzender Sekundär- und Registerdaten stimmten mehr als 90 % der Teilnehmerinnen und Teilnehmer zu. DISKUSSION: Die Bereitschaft, möglichst alle Untersuchungsmodule durchzuführen, war trotz des zeitlichen Aufwandes außerordentlich hoch. Dadurch wird die NAKO zu einer zentralen Ressource für die epidemiologische Forschung in Deutschland. Sie wird es ermöglichen, neue Strategien zur Früherkennung, Vorhersage und Primärprävention chronischer Krankheiten zu entwickeln.

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.

National mortality statistics commonly provide disease-specific absolute and relative frequencies of death by sex and age, but not by exposure status. However, it is often of interest to know how many of the diseased individuals, that is the cases, were exposed or not exposed to a specific risk factor. We present two methods to estimate the proportion and the number of exposed and nonexposed cases, both of which require an estimate of the exposure prevalence in the nondiseased population. Method I additionally requires an estimate of the relative effect of exposure, that is a relative risk function if the exposure has a continuous distribution, or a relative risk estimate for each category if the exposure is categorical. Method II additionally requires an estimate of the disease rate among the nonexposed. We provide theoretical justifications, discuss practical limitations, and provide an R script to calculate the probability for nonexposure among the diseased, and compare the approaches. Both methods are subsequently applied to the estimation of the number of never smokers among lung cancer deaths. The two suggested methods rely on the availability of specific data sources and might therefore be applicable in different research settings. Both methods yield unbiased estimates of the number of nonexposed cases, given that the respective underlying assumptions are fulfilled.

BACKGROUND: Caries and periodontitis are highly prevalent worldwide. Because detailed data on these oral diseases were collected within the framework of the German National Cohort (GNC), associations between oral and systemic diseases and conditions can be investigated. OBJECTIVES: The study protocol for the oral examination was designed to ensure a comprehensive collection of dental findings by trained non-dental staff within a limited examination time. At the mid-term of the GNC baseline examination, a first quality evaluation was performed to check the plausibility of results and to propose measures to improve the data quality. MATERIALS AND METHODS: A dental interview, saliva sampling and oral diagnostics were conducted. As part of the level‑1 examination, the number of teeth and prostheses were recorded. As part of the level‑2 examination, detailed periodontal, cariological and functional aspects were examined. All examinations were conducted by trained non-dental personnel. Parameters were checked for plausibility and variable distributions were descriptively analysed. RESULTS: Analyses included data of 57,967 interview participants, 56,913 level‑1 participants and 6295 level‑2 participants. Percentages of missing values for individual clinical parameters assessed in level 1 and level 2 ranged between 0.02 and 3.9%. Results showed a plausible distribution of the data; rarely, implausible values were observed, e.g. for measurements of horizontal and vertical overbite (overjet and overbite). Intra-class correlation coefficients indicated differences in individual parameters between regional clusters, study centres and across different examiners. CONCLUSIONS: The results confirm the feasibility of the study protocol by non-dental personnel and its successful integration into the GNC’s overall assessment program. However, rigorous dental support of the study centres is required for quality management. HINTERGRUND:Karies und Parodontitis sind weltweit hoch prävalente Erkrankungen. Durch ihre Erfassung im Rahmen der NAKO Gesundheitsstudie können Assoziationen zwischen oralen und systemischen Erkrankungen untersucht werden. FRAGESTELLUNG: In einer ersten Qualitätsanalyse zur Halbzeit der NAKO-Basiserhebung wird die Plausibilität der zahnmedizinischen Ergebnisse überprüft. Es werden Maßnahmen zur Verbesserung der Datenqualität vorgeschlagen. MATERIAL UND METHODEN: Ein zahnmedizinisches Interview, eine Speichelprobengewinnung und eine Befunderhebung wurden durchgeführt. Im Rahmen der Level-1-Untersuchung wurden Zahn- und Prothesenanzahl erfasst. In der Level-2-Untersuchung wurden detaillierte parodontologische, kariologische und funktionelle Befunde erhoben. Alle Untersuchungen wurden von geschultem nichtzahnmedizinischen Personal durchgeführt. Es wurden Plausibilitätsprüfungen durchgeführt sowie Verteilungen deskriptiv dargestellt. ERGEBNISSE: In die Analysen gingen Daten von 57.967 Interviewteilnehmer*innen, 56.913 Level-1- und 6295 Level-2-Teilnehmer*innen ein. Der Anteil fehlender Werte lag für die einzelnen Parameter der Level-1- und Level-2-Untersuchungen zwischen 0,02 % und 3,9 %. Die Parameter zeigten eine plausible Verteilung; vereinzelt wurden unplausible Werte beobachtet, z. B. beim horizontalen und vertikalen Überbiss (Overjet und Overbite). Anhand der Intraklassenkorrelationskoeffizienten wurden für die einzelnen Parameter Unterschiede zwischen regionalen Clustern, den Studienzentren und verschiedenen Untersucher*innen nachgewiesen. DISKUSSION: Die bisherigen Ergebnisse bestätigten die Umsetzbarkeit des Studienprotokolls durch nichtzahnmedizinisches Personal und die erfolgreiche Integration in das Untersuchungsprogramm der NAKO Gesundheitsstudie. Die Studienzentren benötigen eine intensive zahnmedizinische Betreuung für das Qualitätsmanagement.

BACKGROUND: Infectious diseases continue to play an important role for disease perception, health-economic considerations and public health in Germany. In recent years, infectious diseases have been linked to the development of non-communicable diseases. Analyses of the German National Cohort (GNC) may provide deeper insights into this issue and pave the way for new targeted approaches in disease prevention. OBJECTIVES: The aim was to describe the tools used to assess infectious diseases and to present initial data on infectious disease frequencies, as well as to relate the GNC assessment tools to data collection methods in other studies in Germany. METHODS: As part of the baseline examination, questions regarding infectious diseases were administered using both an interview and a self-administered touchscreen questionnaire. Data from the initial 101,787 GNC participants were analysed. RESULTS: In the interview, 0.2% (HIV/AIDS) to 8.6% (shingles) of respondents reported ever having a medical diagnosis of shingles, postherpetic neuralgia (in cases where shingles was reported), hepatitis B/C, HIV/AIDS, tuberculosis or sepsis if treated in hospital. In the questionnaire, 12% (cystitis) to 81% (upper respiratory tract infections) of respondents reported having experienced at least one occurrence of upper or lower respiratory tract infections, gastrointestinal infections, cystitis or fever within the past 12 months. OUTLOOK: The cross-sectional analyses of data and tools presented here – for example on determinants of susceptibility to self-reported infections – can be anticipated from the year 2021 onward. Beyond that, more extensive research into infectious disease epidemiology will follow, particularly once analyses of GNC biological materials have been performed. HINTERGRUND: Infektionen spielen für das Krankheitsempfinden, für gesundheitsökonomische Überlegungen sowie Public Health in Deutschland weiterhin eine wichtige Rolle. Sie wurden in den letzten Jahren außerdem mit der Entstehung von nichtübertragbaren Erkrankungen in Zusammenhang gebracht. Die NAKO Gesundheitsstudie kann Erkenntnisse auf diesem Gebiet vertiefen und damit zielgenaueren präventiven Ansätzen den Weg bereiten. ZIEL: Die infektionsbezogenen Erhebungsinstrumente sollen beschrieben und in Bezug zu Erhebungsarten anderer deutscher Studien gesetzt werden. Zudem werden erste Daten zur Häufigkeit von Infektionskrankheiten berichtet. METHODEN: Fragen zu Infektionskrankheiten wurden in der NAKO-Basiserhebung sowohl im Interview als auch im Selbstausfüllerfragebogen (Touchscreen) gestellt. Es wurden die Daten der ersten 101.787 Teilnehmenden ausgewertet. ERGEBNISSE: Das Auftreten von Herpes Zoster (HZ), Post-Zoster-Neuralgie (bei Angabe von HZ), Hepatitis B/C, HIV/Aids und Tuberkulose im Sinne einer ärztlichen Diagnose bzw. von Sepsis als Grund für eine stationäre Behandlung wurde von 0,2 % (HIV/Aids) bis 8,6 % (HZ) der Befragten im Interview angegeben. Im Touchscreenmodul wurde das mindestens einmalige Auftreten einer Infektion der oberen Atemwege (IOA), der unteren Atemwege, des Magen-Darm-Traktes, der Harnblase oder von Fieber in den letzten 12 Monaten von 12 % (Zystitis) bis 81 % (IOA) berichtet. AUSBLICK: Weitere Ergebnisse anhand von Daten aus den hier vorgestellten Fragebögen sind im Querschnittsdesign – beispielsweise zu Determinanten der Anfälligkeit für selbst berichtete Infektionen – ab 2021 zu erwarten. Die Bearbeitung darüber hinausgehender Forschungsfragen der Infektionsepidemiologie wird insbesondere nach Analysen von NAKO-Bioproben möglich sein.

BACKGROUND: Asthma is one of the most common chronic diseases in both children and adults. Asthma first occurring in adulthood (adult-onset asthma, AOA) is associated with poorer prognosis compared to childhood-onset asthma (COA), which urgently calls for more research in this area. The aim of this work was to analyze the data on asthma collected in the German National Cohort and compare it with the German Health Interview and Examination Survey for Adults (DEGS), in particular regarding AOA. MATERIAL AND METHODS: Our analysis was based on the dataset of the main questionnaire at mid-term of the German National Cohort baseline examination, comprising 101,723 participants. Variables considered in the analyses were self-reported diagnosis of asthma, age at first diagnosis, asthma treatment in the past 12 months, age, and sex. RESULTS: In the midterm dataset, 8.7% of women and 7.0% of men in the German National Cohort reported that they had ever been diagnosed with asthma. Approximately one third of participants with asthma received their initial diagnosis before their 18th birthday. COA affected 2.2% of women and 2.8% of men, whereas AOA affected 6.5% of women and 4.2% of men. During the previous 12 months, 33% of COA cases and 60% of AOA cases were medically treated. CONCLUSION: The proportion of persons affected by asthma in the German National Cohort, as well as observed patterns regarding age and gender, corresponds to other data sources such as DEGS. However, in our analysis, the proportion of individuals with AOA was higher than described in the literature. The increase in cumulative asthma diagnoses with age is markedly steeper in younger participants, indicating a rising trend over time. HINTERGRUND: Asthma bronchiale stellt über alle Bildungsschichten hinweg eine der häufigsten chronischen Erkrankungen im Kindes- und Erwachsenenalter dar. Im Erwachsenenalter erstmals auftretendes Asthma (Adult-onset Asthma, AOA) ist im Vergleich zu Childhood-onset Asthma (COA) mit einer schlechteren Prognose assoziiert, was verstärkte Untersuchungen in diesem Bereich erfordert. Ziel der Arbeit war es, Häufigkeiten und das Alter bei Erstdiagnose aus Selbstangaben zu Asthma bei Erwachsenen in der NAKO Gesundheitsstudie darzustellen und mit Daten der Studie zur Gesundheit Erwachsener in Deutschland (DEGS) zu vergleichen. MATERIAL UND METHODEN: Unsere Analyse beruht auf einem Datensatz zur Halbzeit der NAKO-Basiserhebung mit 101.284 Personen. Verwendete Variablen waren die Selbstangabe zum jemals ärztlich diagnostizierten Asthma, Alter bei Erstdiagnose, Behandlung in den letzten 12 Monaten, Alter und Geschlecht. ERGEBNISSE: Laut Datenbasis zur Halbzeit berichteten in der NAKO 8,7 % der Frauen und 7,0 % der Männer, dass bei ihnen jemals Asthma diagnostiziert wurde. Etwa bei einem Drittel der Teilnehmenden mit Asthma wurde die Diagnose bereits im Kindes‑/Jugendalter (

Die körperliche Fitness ist das Maß für die individuelle Fähigkeit, körperlich aktiv zu sein. Ihre wesentlichen Komponenten sind die kardiorespiratorische Fitness (Cardiorespiratory Fitness, CRF), die Muskelkraft und die Beweglichkeit. Neben der körperlichen Aktivität ist die körperliche Fitness ein wesentlicher Prädiktor für Morbidität und Mortalität. Ziel der Arbeit sind die Beschreibung der Erhebungsmethoden körperlicher Fitness in der NAKO Gesundheitsstudie und die Darstellung erster deskriptiver Ergebnisse. In der NAKO-Basiserhebung wurden die maximale Handgreifkraft (Grip Strength, GS) und die CRF als Komponenten der körperlichen Fitness über ein Handdynamometer bzw. über einen Fahrradergometertest mit submaximaler Belastung erhoben. Daraus wurde die maximale Sauerstoffaufnahme (VO2max) zur Beurteilung der CRF abgeleitet. Die Ergebnisse von insgesamt 99.068 GS-Messungen und 3094 Messungen der CRF beruhen auf einem Datensatz zur Halbzeit der Basiserhebung der NAKO (Alter 20–73 Jahre, 47 % Männer). Männer zeigten im Vergleich zu Frauen höhere Werte der körperlichen Fitness (Männer: GS = 47,8 kg, VO2max = 36,4 ml·min−1 · kg−1; Frauen: GS = 29,9 kg, VO2max = 32,3 ml·min−1 · kg−1). Ungefähr ab dem 50. Lebensjahr konnte ein Rückgang der GS verzeichnet werden, wohingegen die CRF ab der Altersgruppe 20–29 Jahre bis zu den ≥60-Jährigen kontinuierlich abfiel. Die GS und die VO2max zeigten nach Korrektur für das Körpergewicht einen linear positiven Zusammenhang (Männer β = 0,21; Frauen β = 0,35). Die Analysen zeigten eine gute Übereinstimmung der Verteilung der körperlichen Fitness in der NAKO im Vergleich zu anderen bevölkerungsbasierten Studien. Zukünftige Auswertungen werden insbesondere die unabhängige Bedeutung der GS und CRF bei der Prädiktion von Morbidität und Mortalität beleuchten. Physical fitness is defined as an individual’s ability to be physically active. The main components are cardiorespiratory fitness (CRF), muscle strength, and flexibility. Regardless of physical activity level, physical fitness is an important determinant of morbidity and mortality. The aim of the current study was to describe the physical fitness assessment methodology in the German National Cohort (NAKO) and to present initial descriptive results in a subsample of the cohort. In the NAKO, hand grip strength (GS) and CRF as physical fitness components were assessed at baseline using a hand dynamometer and a submaximal bicycle ergometer test, respectively. Maximum oxygen uptake (VO2max) was estimated as a result of the bicycle ergometer test. The results of a total of 99,068 GS measurements and 3094 CRF measurements are based on a data set at halftime of the NAKO baseline survey (age 20–73 years, 47% men). Males showed higher values of physical fitness compared to women (males: GS = 47.8 kg, VO2max = 36.4 ml·min−1 · kg−1; females: GS = 29.9 kg, VO2max = 32.3 ml · min−1 · kg−1). GS declined from the age of 50 onwards, whereas VO2max levels decreased continuously between the age groups of 20–29 and ≥60 years. GS and VO2max showed a linear positive association after adjustment for body weight (males β = 0.21; females β = 0.35). These results indicate that the physical fitness measured in the NAKO are comparable to other population-based studies. Future analyses in this study will focus on examining the independent relations of GS and CRF with risk of morbidity and mortality.

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer. ispartof: JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE vol:113 issue:3 pages:329-337 ispartof: location:United States status: published

BACKGROUND: Data on self-reported cardiovascular and metabolic diseases are available for the first 100,000 participants of the population-based German National Cohort (GNC, NAKO Gesundheitsstudie). OBJECTIVES: To describe assessment methods and the frequency of self-reported cardiovascular and metabolic diseases in the German National Cohort. MATERIALS AND METHODS: Using a computer-based, standardized personal interview, 101,806 participants (20–75 years, 46% men) from 18 nationwide study centres were asked to use a predefined list to report medical conditions ever diagnosed by a physician, including cardiovascular or metabolic diseases. For the latter, we calculated sex-stratified relative frequencies and compared these with reference data. RESULTS: With regard to cardiovascular diseases, 3.5% of men and 0.8% of women reported to have ever been diagnosed with a myocardial infarction, 4.8% and 1.5% with angina pectoris, 3.5% and 2.5% with heart failure, 10.1% and 10.4% with cardiac arrhythmia, 2.7% and 1.8% with claudicatio intermittens, and 34.6% and 27.0% with arterial hypertension. The frequencies of self-reported diagnosed metabolic diseases were 8.1% and 5.8% for diabetes mellitus, 28.6% and 24.5% for hyperlipidaemia, 7.9% and 2.4% for gout, and 10.1% and 34.3% for thyroid diseases. Observed disease frequencies were lower than reference data for Germany. CONCLUSIONS: In the German National Cohort, self-reported cardiovascular and metabolic diseases diagnosed by a physician are assessed from all participants, therefore representing a data source for future cardio-metabolic research in this cohort. HINTERGRUND: Aus der NAKO Gesundheitsstudie, der größten deutschen bevölkerungsbasierten Studie zur Gesundheit, liegen die Daten zu selbst berichteten kardiovaskulären und metabolischen Erkrankungen der ersten ca. 100.000 Teilnehmenden vor. ZIEL: Beschreibung der Methoden zur Erhebung sowie Berechnung der Häufigkeit kardiovaskulärer und metabolischer Erkrankungen in der NAKO. MATERIAL UND METHODEN: 101.806 Teilnehmende (20–75 Jahre, 46 % Männer) aus 18 bundesweiten Studienzentren wurden in einem computergestützten, standardisierten persönlichen Interview gebeten, anhand einer vorgegebenen Liste anzugeben, welche Erkrankungen bei ihnen jemals ärztlich diagnostiziert wurden, darunter auch kardiovaskuläre und metabolische Erkrankungen. Für Letztere wurden deren geschlechtsspezifische relative Häufigkeiten berechnet und diese mit Referenzzahlen verglichen. ERGEBNISSE: Bezogen auf die kardiovaskulären Erkrankungen berichteten 3,5 % der Männer und 0,8 % der Frauen, jemals einen Herzinfarkt diagnostiziert bekommen zu haben, 4,8 % bzw. 1,5 % eine Angina pectoris, 3,5 % bzw. 2,5 % eine Herzinsuffizienz, 10,1 % bzw. 10,4 % Herzrhythmusstörungen, 2,7 % bzw. 1,8 % eine Claudicatio intermittens und 34,6 % bzw. 27,0 % eine arterielle Hypertonie. Die Häufigkeit berichteter diagnostizierter metabolischer Erkrankungen lag bei 8,1 % bzw. 5,8 % für Diabetes mellitus, bei 28,6 % bzw. 24,5 % für Hyperlipidämie, bei 7,9 % bzw. 2,4 % für Gicht und bei 10,1 % bzw. 34,3 % für Schilddrüsenerkrankungen. Die beobachteten Häufigkeiten lagen insgesamt etwas niedriger als Vergleichsdaten für Deutschland. DISKUSSION: Die NAKO erhebt von allen Teilnehmenden selbst berichtete, ärztlich diagnostizierte kardiovaskuläre und metabolische Erkrankungen und stellt damit eine Datenressource für weitergehende kardiometabolische Forschungsfragestellungen dar.

HINTERGRUND: Arterielle Hypertonie ist einwichtiger Risikofaktor für Herz-Kreislauf-Er-krankungen. Epidemiologische Studien führen meist drei konsekutive Blutdruckmessungen durch. Der 1. Messwert wird für Auswertungen verworfen, da dieser am stärksten durch vorhergehende Aktivitäten beeinflusst sein kann. Aus zeitlichen Gründen wurden in der NAKO Gesundheitsstudie nur zwei Messungen durchgeführt. FRAGESTELLUNG: Die vorliegende Analyse untersucht Auswirkungen methodischer Unterschiede bei der Blutdruckmessungauf die Hypertoniehäufigkeit und mittlere Blutdruckwerte anhand eines Vergleichsder ersten Hälfte der NAKO-Teilnehmenden(nur 2 Messungen) mit 5 deutschen populationsbasierten Studien (3 Messungen). MATERIAL UND METHODEN: Es wurden Daten der Teilnehmenden aus der NAKO (erste 101.816 Personen), der bundesweiten Studie zur Gesundheit Erwachsener des Robert Koch-Instituts (DEGS1) und aus 4 regionalen populationsbasierten Kohortenstudien (CARLA, HNR, KORA, SHIP) analysiert. Alters- und geschlechtsspezifische mittlere Blutdruckwerte und Hypertoniehäufigkeiten wurden auf Basis des 2. Messwertes, des Mittelwerts aus 1. und 2. sowie aus 2. und 3. Messung berechnet. ERGEBNISSE: Die mittleren Blutdruckwerte der beiden aktuellsten Studien (NAKO und DEGS1) sind sehr ähnlich und niedriger als in den anderen Studien. Die Differenz zwischen dem 2. Messwert und dem Mittelwert aus 2. und 3. Messung ist gering (maximale mittlere Abweichung: 1,5mmHg systolisch), jedoch ist die mittels des 2. Messwertes berechnete Hypertoniehäufigkeit der Bevölkerung höher als bei Verwendung des Mittelwertsaus 2. und 3. Messung. DISKUSSION: Die Ergebnisse der vorliegenden Analyse zeigen, dass für die wissenschaftliche Auswertung der NAKO-Daten die Verwendung des 2. Blutdruckmesswerts zu empfehlen ist. BACKGROUND: Arterial hypertension is an important risk factor for cardiovascular diseases. Epidemiological studies typically perform three consecutive blood pressure measurements. The first measurement is discarded in subsequent analyses, as this value may be strongly affected by previous activities. Due to time constraints the German National Cohort (GNC NAKO) performed only two blood pressure measurements. OBJECTIVES. The present analysis examined the possible effects of methodological differences in blood pressure measurement by comparing the first 101,816 GNC participants (two blood pressure measurements) with those of five German population-based studies (three measurements). MATERIALS AND METHODS: Blood pressure data from participants aged 20 to 79 years from the GNC, the German Health Interview and Examination Survey for Adults by the Robert Koch Institute (DEGS1), and four regional population-based cohort studies (CARLA, HNR, KORA, SHIP) were used to calculate age-and sex-specific mean blood pressure values and hypertension frequencies based on the second blood pressure measurement, the arithmetic mean of the first and second value and of the second and third (the latter not available in the GNC). RESULTS: The mean blood pressure values of the two most recent studies (GNC, DEGS1) were very similar and lower than in the other studies. The difference of the second measurement and the mean of second and third measurement was small (maximum mean difference: 1.5mmHg systolic blood pressure), but leads to higher estimated hypertension frequencies. CONCLUSIONS: The current results show that using the second blood pressure measurement should be recommended for scientific analyses of GNC data.

BACKGROUND: Caesarean section (CS) has been associated with an increased risk of type 1 diabetes (T1D). The lack of exposure to maternal vaginal and anal microbiome and bypassing the labor process often observed in elective CS may affect neonatal immune system development. This study aims to summarize the effects of elective and non-elective CS on T1D risk in the offspring.METHODS: A systematic literature search was conducted online for publications providing data on elective and non-elective CS with T1D diagnosis in children and young adults, followed by a meta-analysis from selected studies. Newcastle-Ottawa Scale and GRADEpro tool were applied for quality analysis.RESULTS: Nine observational studies comprising over 5 million individuals fulfilled the inclusion criteria. Crude OR estimates showed a 12% increased T1D risk from elective CS compared to vaginal delivery with significant heterogeneity. Adjusted ORs from seven studies did not show T1D risk differences from either CS category, and heterogeneity was detected between studies. Separate analysis of cohort and case-control studies reduced the heterogeneity and revealed a slight increase in T1D risk associated with elective CS in cohort studies (adjusted OR = 1.12 (1.01-1.24)), and a higher increased risk associated with non-elective CS in case-control studies (adjusted OR = 1.19 (1.06-1.34)).CONCLUSION: Summarized crude risk estimates showed a small increased T1D risk in children and young adults born through elective CS compared to vaginal delivery, but with significant heterogeneity. Adjusted risk estimates by study design indicated a slightly increased T1D risks associated with elective or non-elective CS.

Lignans are associated with improved postmenopausal breast cancer (BC) survival, but whether these associations, particularly with enterolactone (major lignan metabolite), persist over time is unclear. Little is known about other phytoestrogens on prognosis in long-term survivors. The study examines associations of prognosis with 1) circulating postdiagnosis enterolactone, 2) eight circulating phytoestrogen metabolites, and 3) changes in enterolactone and genistein. In a German cohort of 2,105 postmenopausal BC patients with blood samples collected at recruitment 2002-2005 (baseline) and re-interview in 2009 (follow-up), delay-entry Cox proportional hazards regression was used. Landmark analysis showed that circulating enterolactone (log2) associations with 5-year survival changed over time, with strongest hazard ratios of 0.89 (95% CI, 0.80-0.99) at blood draw (BD) and 0.86 (0.77-0.97) at 2 years post-BD for BC mortality, and 0.87 (0.80-0.95) at BD and 0.84 (0.76-0.92) at 3 years post-BD for all-cause mortality, which attenuated thereafter. In long-term survivors, increasing concentrations of genistein (1.17, 1.01-1.36), resveratrol (1.19, 1.02-1.40), and luteolin (1.96, 1.07-3.58) measured in follow-up blood samples were associated with poorer subsequent prognosis. Neither enterolactone at follow-up nor changes in enterolactone/genistein were associated with prognosis. Large long-term longitudinal studies with multiple phytoestrogen measurements are required to understand long-term effects of phytoestrogens after BC.

Introduction: Up to now,reliable results regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with multiple myeloma (MM), especially under current myeloma-directed therapy, are scarcely available. Here, we report an analysis describing the level of post-vaccination antibody titers after the 1 stand 2 ndanti-SARS-CoV-2 vaccination depending on therapy, remission status, and B- and T-cell numbers in patients with MM and related plasma cell neoplasia. Methods: This observational single-center study included patients aged ≥18 years with diagnoses of MM, monoclonal gammopathies of clinical significance (MGCS), or systemic light-chain amyloidosis (AL) who were eligible for Anti-SARS-CoV-2 vaccination according to the International Myeloma Society recommendations. Patients with prior COVID-19 infections were excluded. Samples were analyzed for the presence of SARS-CoV-2 specific antibodies using the quantitative anti-spike IgG (SARS-CoV-2 spike RBD IgG, cut off ≥ 0.8 BAU/ml) according to manufacturer's recommendations. SARS-CoV-2 spike protein antibody titer (SP-AbT) were evaluated after at least 7 days after the 1 stand 2 ndvaccination, respectively. This study was performed between January 1 - July 15, 2021, at the University Medical Center Hamburg-Eppendorf, Germany, as part of the COVIDOUT trial (NCT04779346). All patients provided written informed consent. Aims of this study were to evaluate a possible correlation between SP-AbT and CD19+ B lymphocyte count, as well as to identify other factors impacting vaccination response. Results: 82 patients who received SARS-CoV-2 vaccines (including 67 patients with mRNA-, 8 with vector-based vaccines and 4 heterologous vaccinations) were included. 74 patients had diagnosis of MM, 4 of MGCS/smoldering MM and 4 of AL. Median age was 68 years (range 35-85) and 49 patients were male. In total, 37 patients (45.1%) received anti-CD38- and 2 (2.4%) anti-SLAMF7-targeting therapies at the time of vaccination, 52 (63.4%) patients received immunomodulatory drug (IMID)-based treatments and 13 patients (15.9%) were under active surveillance. 59% of patients had newly diagnosed and 41% refractory or relapsed disease. In total, 75.6% of all patients were in deep remissions (very good partial remission or better). Assessment of anti-SARS-CoV-2 antibody titers took place in median 23 days (range [r] 8-63 days) after the 1 stand 21 days (r: 6-53) after the 2 ndvaccination. A positive SARS-CoV-2 SP-AbT was detected in 31.9% of assessable patients with an overall median SP-AbT of 0 BAU/ml (r: 0-10328, mean 202.36) after the 1 stvaccination and increased up to 88.9% (median SP-AbT of 216.87 BAU/ml, r: 0-25720, mean 2139.29) after 2 ndvaccination. Of the patients not showing positive SP-AbT after the 1 stvaccination, 80.9% became positive after 2 ndvaccination, while 19.1 % remained negative. Median SP-AbT titer was significantly lower compared to patients who became positive already after 1 stvaccination (51.04 vs. 2191.87 BAU/ml, p Conclusions: In spite of immunodeficiency and immunosuppressive therapy, most MM patients develop SP-AbT. However, about 11% of MM patients failed to develop SP-AbT after full vaccination, and thus remain on risk for COVID-19. Higher counts of CD19+ B lymphocytes, with a threshold of 30 CD19+ B lymphocytes/µl, are predictive for SP-AbT formation and may further help to identify patients at higher risk of insufficient vaccination response in whom control of vaccination success and potential third vaccination are particularly important. Disclosures Bokemeyer: GlaxoSmithKline: Research Funding; Inside: Research Funding; IO Biotech: Research Funding; Eisai: Research Funding; Daiichi Sankyo: Research Funding; Gilead Sciences: Research Funding; Blueprint Medicine: Research Funding; BerGenBio: Research Funding; Janssen-Cilag: Research Funding; Isofol Medical: Research Funding; AOK Health insurance: Consultancy; GSO: Consultancy; Bayer Schering Pharma: Consultancy; Gylcotope GmbH: Research Funding; ADC Therapeutics: Research Funding; Apellis Pharmaceuticals: Research Funding; Amgen: Research Funding; Alexion Pharmaceuticals: Research Funding; Agile Therapeutics: Research Funding; Merck Serono: Consultancy, Other: Travel accomodation ; Lilly/ImClone: Consultancy; Merck Sharp Dohme: Consultancy, Honoraria; AstraZeneca: Honoraria, Research Funding; BMS: Honoraria, Other: Travel accomodation, Research Funding; Bayer: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Other: Travel accomodation; Merck KGaA: Honoraria; Abbvie: Research Funding; Boehringer Ingelheim: Research Funding; Celgene: Research Funding; Astellas: Research Funding; Karyopharm Therapeutics: Research Funding; Lilly: Research Funding; Millenium: Research Funding; MSD: Research Funding; Nektar: Research Funding; Rafael Pharmaceuticals: Research Funding; Springworks Therapeutics: Research Funding; Taiho Pharmaceutical: Research Funding; Pfizer: Other. Sinn: Incyte: Honoraria, Research Funding; Pfizer: Honoraria; Servier: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Research Funding; Astra Zenica: Consultancy, Research Funding; MSD: Consultancy, Research Funding; Sanofi: Consultancy; Bayer: Research Funding; BMS: Honoraria, Research Funding. Leypoldt: GSK: Consultancy, Other: Meeting attendance ; Sanofi: Consultancy; Abbvie: Other: Meeting attendance . Weisel: Adaptiv Biotec: Consultancy; Abbvie: Consultancy; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Karyopharm: Honoraria; Novartis: Honoraria; Oncopeptides: Consultancy, Honoraria; Pfizer: Honoraria; Roche: Honoraria; Takeda: Honoraria; Sanofi: Consultancy, Honoraria, Research Funding.

Introduction Previous studies in African countries have been suggestive of non-specific effects (NSE) of vaccination on child survival. Live vaccines (e.g. measles, MV) have been found to reduce child mortality while inactivated vaccines (e.g. diphtheria-tetanus-pertussis, DTP) have been associated with increased mortality; NSE were often found to be sex-specific. Methods A case-control study nested into the Health and Demographic Surveillance System (HDSS) cohort of the Centre de Recherche en Sante de Nouna (CRSN) was conducted in northwestern Burkina Faso. A total of 3,010 children born in 2009–11, were included in the study, 375 cases and 2635 age and village matched controls. The main outcome measures were the mortality odds ratios for vaccinated versus unvaccinated children by antigen. The main outcome measures were the mortality odds ratios for vaccinated versus unvaccinated children by antigen. Results Most deaths occurred in late infancy, and there were significantly more deaths in males as compared to females (OR 1.29, CI 1.04–1.60). Overall, there was no statistically significant association between vaccine status and mortality. However, among children in the age group 2–8 months, there was a consistent sex-differential pattern for all doses of oral polio vaccine combined with pentavalent vaccine (OPV + Penta), with the vaccines being associated with lower mortality in boys, but not in girls. Routine MV + yellow fever vaccine was associated with reduced mortality, but only before mass vaccination campaigns with meningitis and measles vaccines took place. Conclusions The findings of this study provide further support on the existence of NSE of childhood vaccinations in a large population of rural Burkina Faso. More randomized controlled trials are needed to confirm these observations.