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Although “post-COVID-19 syndrome” (PCS) is reported to be common even in non-hospitalized individuals, long-term information on symptom burden, healthcare needs, utilization, and satisfaction with healthcare is scarce. The objectives of this study were to describe symptom burden, healthcare utilization and experiences with the healthcare offered for PCS in a German sample of non-hospitalized persons 2 years after SARS-CoV-2 infection. Individuals with past COVID-19 confirmed by positive polymerase chain reaction testing were examined at the University Hospital of Augsburg from 4 November 2020 to 26 May 2021 and completed a postal questionnaire between 14 June 2022 and 1 November 2022. Participants who self-reported the presence of fatigue, dyspnea on exertion, memory problems or concentration problems were classified as having PCS. Of the 304 non-hospitalized participants (58.2% female, median age 53.5), 210 (69.1%) had a PCS. Among these, 18.8% had slight to moderate functional limitations. Participants with PCS showed a significantly higher utilization of healthcare and a large proportion complained about lacking information on persistent COVID-19 symptoms and problems finding competent healthcare providers. The results indicate the need to optimize patient information on PCS, facilitate access to specialized healthcare providers, provide treatment options in the primary care setting and improve the education of healthcare providers.

Background Post-COVID-Fatigue (PCF) is one of the most reported symptoms following SARS-CoV-2 infection. Currently, research on persistent symptoms focuses mainly on severe infections, while outpatients are rarely included in observations. Objective To investigate whether the severity of PCF is related to the number of acute and persistent symptoms due to mild-to-moderate COVID-19 and to compare the most common symptoms during acute infection with the persistent symptoms in PCF patients. Methods A total of 425 participants were examined after COVID-19 treated as an outpatient (median 249 days [IQR: 135; 322] after acute disease) at the site of University Hospital Augsburg, Germany. The Fatigue Assessment Scale (FAS) was used to quantify the severity of PCF. The number of symptoms (maximum 41) during acute infection and persistent symptoms (during the last 14 days before examination) were added up to sum scores. Multivariable linear regression models were used to show the association between the number of symptoms and PCF. Results Of the 425 participants, 37% (n = 157) developed PCF; most were women (70%). The median number of symptoms was significantly higher in the PCF group than in the non-PCF group at both time points. In multivariable linear regression models, both sum scores were associated with PCF (acute symptoms: β-estimate per additional symptom [95%-CI]: 0.48 [0.39; 0.57], p p Conclusion Each additional symptom that occurs in COVID-19 increases the likelihood of suffering a higher severity of PCF. Further research is needed to identify the aetiology of PCF. Trial registration: Nr. NCT04615026. Date of registration: November 4, 2020.

Supplementary Tables 1S-7S, Figure 1S from Haplotype Analysis of the HSD17B1 Gene and Risk of Breast Cancer: A Comprehensive Approach to Multicenter Analyses of Prospective Cohort Studies

Understanding the adverse effects of proton pump inhibitors (PPIs) is important due to their widespread use, but the available evidence for an increased dementia risk amongst patients taking PPIs is inconclusive. The present study aimed to estimate the causal effect of PPIs on the risk of dementia by target trial emulation and time-varying exposure modeling.Using claims data of 2,698,176 insured people of a large German statutory health insurer, a target trial was conceptualized in which individuals aged 40 years and older were classified as PPI initiators or non-initiators between 2008 and 2018, and were followed until diagnosis of dementia, death, loss to follow-up or end of study. Incidence of dementia (International Classification of Diseases 10 codes F00, F01, F03, F05.1, G30, G31.0, G31.1, G31.9 and F02.8+G31.82) was defined applying a 1-year lag window. Weighted Cox models were used to estimate the effect of PPI initiation versus non-initiation on dementia risk and weighted pooled logistic regression was used to estimate the effect of time-varying use versus non-use.In all, 29,746 PPI initiators (4.4%) and 26,830 non-initiators (1.3%) were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio for dementia was 1.54 (95% confidence interval 1.51-1.58). The hazard ratio for time-dependent PPI use versus non-use was 1.56 (95% confidence interval 1.50-1.63). Differentiated subtypes, including unspecified dementia, Alzheimer's disease and vascular dementia, showed increased risk by PPI initiation and time-varying PPI use.This study suggests that PPI initiation and time-varying PPI use may increase overall dementia risk.

Purpose The German annual drug prescription-report has indicated overuse of proton pump inhibitors (PPIs) for many years; however, little was known about the characteristics of people using PPIs. This study aimed to provide comprehensive utilization data and describe frequencies of potential on- and off-label PPI-indications in Bavaria, Germany. Methods Claims data of statutorily insured people from 2010 to 2018 were used. Defined daily doses (DDDs) of PPIs by type of drug, prevalence of PPI-use and DDDs prescribed per 1000 insured people/day were analyzed. For 2018, proportions of users and DDDs per 1000 insured people were calculated by age and sex. To elucidate changes in prescribing practices due to a suspected drug-drug interaction, we examined co-prescribing of clopidogrel and PPIs between 2010 and 2018. For PPI new users, sums of DDDs and frequencies of potential indications were examined. Results PPI prescribing increased linearly from 2010 to 2016 and gradually decreased from 2016 to 2018. In 2018, 14.7% of women and 12.2% of men received at least one prescription, and 64.8 DDDs (WHO-def.) per 1000 insured people/day were prescribed. Overall, omeprazole use decreased over the observation period and was steadily replaced by pantoprazole, especially when co-prescibed with clopidogrel. An on-label PPI-indication was not reported at first intake in 52.0% of new users. Conclusions The utilization of prescribed PPIs has decreased since 2016. However, a large proportion of new PPI-users had no documentation of a potential indication, and the sums of DDDs prescribed often seemed not to comply with guidelines.

Background: Proton pump inhibitors (PPIs) are well tolerated in the short term but have recently been associated with increased long-term cardiovascular risk in observational studies. Aims: To evaluate long-term risks of myocardial infarction (MI) and ischaemic stroke (IS) associated with PPI vs H2-receptor antagonist (H2RA) therapy in adults without pre-existing cardiovascular or cerebrovascular disease. Methods: Using administrative claims data (2008–2018), we emulated a target trial comparing MI and IS risks in new users of PPIs vs H2RAs. Treatment was identified using dispensed prescriptions. MI and IS were defined using hospital discharge codes. Inverse probability weighting was used to adjust for confounding, and Cox models to estimate hazard ratios (HRs). Survival curves were estimated using weighted Kaplan-Meier estimators. Results: We identified 1143948 new users of PPIs and 36229 new users of H2RAs who were free of prevalent cardiovascular or cerebrovascular disease. The mean follow-up time was 6.2years for PPI initiators and 5.3years for H2RA initiators. After 10years, the HRs for MI and IS were 0.96 (95% confidence interval (CI): 0.80-1.16) and 0.98 (95% CI: 0.89-1.08), respectively. Conclusions: This analysis of claims data of a large German health insurer did not provide evidence that PPI therapy increased the risk of MI or IS in the first decade after treatment initiation.

Several studies have implied a role of magnesium in the development of cardiovascular disease (CVD). Thus, magnesium might serve as a potential risk marker for early CVD. Therefore, we investigated the association of serum magnesium and dietary magnesium intake with markers of subclinical CVD in a population-based study. We used cross-sectional data from the sub-study of the Cooperative Health Research in the Region of Augsburg (KORA-FF4). Markers of subclinical CVD, namely, left and right ventricular structure and function and carotid plaque and carotid wall thickness, were derived by magnetic resonance imaging (MRI). Multivariable-adjusted regression models were applied to assess the relationship between serum and dietary magnesium and MRI-derived subclinical CVD markers. Among 396 included participants (mean age: 56.3 ± 9.2 years; 57.8% male), 181 (45.7%) had low serum magnesium levels (

Nearly all approaches for personalized nutrition (PN) use information, such as the gene variants of individuals, to deliver advice considered more beneficial than generic one-size-fits-all recommendations. Despite great enthusiasm and the increased availability of commercial services, thus far, scientific studies reveal only small to negligible effects on the efficacy and effectiveness of personalized dietary recommendations, even when including genetic or other individual information. In addition, from the public health perspective, scholars criticize PN to primarily target socially privileged groups instead of the general population, which, thereby, potentially widens health inequality. Therefore, we propose to widen the current PN approaches by creating adaptive personalized nutrition advice systems (APNASs) tailored to the type and timing of personalized advice to individual need, capacity, and receptivity in real-life food environments. This concept encompasses a broadening of the current PN goals (i.e., what should be achieved) to incorporate individual goal preferences beyond currently advocated biomedical targets (e.g., making sustainable food choices). Moreover, it covers the personalization processes of behavior change by providing in-situ and just-in-time information in real-life environments (how and when to change), which accounts for individual capacities and constraints (e.g., economic resources). Lastly, it is concerned with a participatory dialogue between individuals and experts when setting goals and deriving measures of adaption. Under this framework, emerging digital nutrition ecosystems enable continuous, real-time monitoring, advice, and support in food environments from exposure to consumption. We present this vision of a novel PN framework together with scenarios and arguments that describe its potential to efficiently address individual and population needs and target groups that may benefit most from such a new PN advice.

Myocardial infarctions (MIs) are a major cause of death worldwide, and both high and low temperatures (i.e. heat and cold) may increase the risk of MI. The relationship between health impacts and climate is complex and influenced by a multitude of climatic, environmental, socio-demographic and behavioural factors. Here, we present a machine learning (ML) approach for predicting MI events based on multiple environmental and demographic variables. We derived data on MI events from the KORA MI registry dataset for Augsburg, Germany, between 1998 and 2015. Multivariable predictors include weather and climate, air pollution (PM10, NO, NO2, SO2 and O3), surrounding vegetation and demographic data. We tested the following ML regression algorithms: decision tree, random forest, multi-layer perceptron, gradient boosting and ridge regression. The models are able to predict the total annual number of MIs reasonably well (adjusted R2=0.62–0.71). Inter-annual variations and long-term trends are captured. Across models the most important predictors are air pollution and daily temperatures. Variables not related to environmental conditions, such as demographics need to be considered as well. This ML approach provides a promising basis to model future MI under changing environmental conditions, as projected by scenarios for climate and other environmental changes.

Limited data on prehospital and early in-hospital coronary heart disease (CHD) deaths is available. Aims of this study were to provide a comprehensive description on CHD cases and to analyse determinants of prehospital death. From a population-based myocardial infarction (MI) registry in Augsburg, Germany we included 12,572 CHD cases aged 25–74 years between 2003–2017 and 4754 CHD cases aged 75–84 years between 2009–2017. Multivariable logistic regression models were conducted to identify patient characteristics associated with prehospital death compared to 28-day survival. In patients aged 25–74 years, 1713 (13.6%) died prehospital, 941 (7.5%) died within the first 24 h in-hospital and 560 (4.5%) died within the 2nd and 28th day after the acute event; in patients aged 75–84 years the numbers were 1263 (26.6%), 749 (15.8%) and 329 (6.9%), respectively. In both age groups increasing age, actual smoking or nicotine abuse, previous MI, angina pectoris and previous stroke were more likely and hypertension was less likely in cases, who died prehospital compared to 28-day survivors. For example, in the 25–74 years old we revealed an adjusted odds ratio (OR) of 4.53 (95% CI 3.84–5.34) for angina pectoris and an OR of 0.69 (95% CI 0.57–0.85) for hypertension. In cases aged 25–74 years, an association of living alone (OR 1.26, 95% CI 1.06–1.49) and diabetes (OR 1.20, 95% CI 1.03–1.41) with prehospital death was found. Whereas in cases aged 75–84 years, chronic obstructive pulmonary disease (OR 2.20, 95%CI 1.69–0.2.85) was associated with prehospital death. In summary, we observed high prehospital and early in-hospital case fatality. Besides classical cardiac risk factors, the impact of living alone on prehospital death was more important in patients aged 25–74 years than in older patients.

IntroductionPsoriasis (PsO), psoriatic arthritis (PsA) and inflammatory bowel disease (IBD), i.e. Crohn’s disease (CD) and ulcerative colitis (UC) are chronic systemic immune-mediated disorders affecting an increasing proportion of adults and children worldwide. Observational studies suggested an association between IBD and PsO and vice versa. However, so far it remains unclear whether a causal relationship exists.MethodsTo investigate the causal paths, a bidirectional two-sample Mendelian randomization (MR) study was conducted using summary statistics from genome-wide association studies (GWASs) including up to 463,372 Europeans. Total and direct effects were derived performing an iterative radial and robust inverse-variance weighted method within the univariable and multivariable MR setting, respectively. Causal estimates were verified using a validation IBD-sample, a series of pleiotropy-robust MR-methods, and sensitivity analyses based on PhenoScanner search in conjunction with network analysis.ResultsGenetically predicted IBD was associated with higher risk of PsO (pooled OR=1.10; 95% CI: (1.05; 1.15); P=1⋅10−4) and PsA (pooled OR=1.10; 95% CI: (1.04; 1.18); P=3⋅10−3). In contrast to UC, the CD subentity was related to PsO (OR=1.16; 95% CI: (1.12; 1.20); P=1⋅10−14) and PsA (OR=1.13; 95% CI: (1.06; 1.20); P=1⋅10−4). Regarding the reverse directions, no notable associations could be found.ConclusionsThis study supports a causal effect between IBD and PsO as well as PsA, but not vice versa. It seems that mainly CD and not UC is responsible for the causal impact of IBD on both psoriasis outcomes. These findings have implications for the management of IBD and psoriasis in clinical practice.

BACKGROUND AND AIMS: Observational research has indicated that proton pump inhibitors (PPIs) might increase the long-term risk of cardiovascular events. This study evaluated the evidence from observational studies for an effect of PPI monotherapy on the risk of incident cardiovascular events and cardiovascular mortality. METHODS: The databases MEDLINE, EMBASE, and Scopus were systematically searched up to September 2021. The primary outcome was first cardiovascular event, i.e. first myocardial infarction or first ischaemic stroke. The secondary outcome was cardiovascular mortality. Studies were included following a detailed risk of bias assessment with the ROBINS-I tool. Sensitivity and bias analyses adjusted for potential publication bias, immortal time bias, and unmeasured confounding. RESULTS: We included ten studies with 75,371 first cardiovascular events, as well as seven studies on cardiovascular mortality with 50,329 cardiovascular deaths in total. The pooled hazard ratios (HRs) for PPI use and cardiovascular events were 1.05 with a 95% confidence interval of (0.96; 1.15) before and 0.99 (0.93; 1.04) after adjusting for observational study design bias. The pooled HRs for PPI use and cardiovascular mortality were 1.27 (1.11; 1.44) before and 1.06 (0.96; 1.16) after adjusting for publication bias and observational study design bias. CONCLUSION: It is questionable, whether PPI monotherapy constitutes a cardiovascular risk factor.

The risk of thromboembolic events is increased for coronavirus disease (COVID)-19 inpatients. For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected outpatients, only few data are available so far.In our prospective single-center study, 461 SARS-CoV-2-infected outpatients were screened for the presence of deep vein thrombosis.Two outpatients had suffered a deep vein thrombosis. An association with previously known risk factors, such as preexisting thrombosis in the medical history or cardiovascular risk factors, could not be proven.General thromboprophylaxis in SARS-CoV-2-infected outpatients is still not recommended.GRUNDLAGEN: Das Risiko für thrombembolische Ereignisse ist für stationäre COVID-19-Patienten erhöht. Für ambulant behandelte SARS-CoV-2-Infizierte liegen bisher nur wenige Daten vor.In der prospektiven Single-Center-Studie der Autoren wurden 461 SARS-CoV-2-Infizierte mit ambulantem Behandlungsverlauf auf das Vorliegen einer tiefen Beinvenenthrombose untersucht.Bei 2 ambulanten Patienten war eine Beinvenenthrombose aufgetreten. Ein Zusammenhang mit bisher bekannten Risikofaktoren, wie vorbestehender Thrombose in der Anamnese oder kardiovaskulären Risikofaktoren, konnte nicht nachgewiesen werden.Eine generalisierte Thromboseprophylaxe bei ambulanten SARS-CoV-2-Infizierten wird weiterhin nicht empfohlen.

Purpose The Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire is the only existing disease-specific instrument for measuring quality of life after pulmonary embolism (PE). It includes six dimensions: frequency of complaints, limitations in activities of daily living, work-related problems, social limitations, intensity of complaints and emotional complaints. The present study aimed to determine the psychometric properties including responsiveness and structural validity of the German version. Methods The analysis used data from participants of the LEA cohort study at University Hospital Augsburg. The PEmb-QoL was administered via postal surveys 3, 6 and 12 months post-PE. Internal consistency and test–retest reliability were evaluated by calculating Cronbach’s alpha and intra-class correlation coefficients (ICC). Standardized response means (SRM) were calculated for investigating responsiveness. For evaluating the fit of the factor structure, confirmatory factor analysis (CFA) was conducted. Results Overall, we used data from 299 patients 3 months after PE. Cronbach’s alpha (0.87–0.97) and ICC (0.53–0.90) were in an acceptable to good range. SRM scores showed good responsiveness of all dimensions. CFA revealed the four-factor model including one general factor to have a good model fit. Conclusion Despite existing floor effect, most standard criteria of reliability and validity were met and indications for appropriateness of the PEmb-QoL summary score could be found. Apart from some restrictions concerning the factor structure and the dimension of social limitations, our results support the use of the PEmb-QoL questionnaire for evaluating PE-specific quality of life. Future studies should seek replication in different samples to ensure generalizability of the findings.

Approximately one-third of patients with stroke show depressive symptoms. The so-called post-stroke depression (PSD) has a negative influence on mortality as well as physical and mental conditions. The aim of this study was to analyse the association between PSD and health-related quality of life (HRQOL) in patients with stroke. The analysis was based on data of 326 patients from the Stroke Cohort Augsburg (SCHANA Study) collected after the stroke event by interview and three months later using a postal survey. Depressive symptoms were measured with the Patient-Health Questionnaire (PHQ-9), subjective health status with the EuroQol 5D visual analogue scale (EQ-5D VAS), and HRQOL with the Stroke Impact Scale (SIS). Patients with depressive symptoms were compared to those without depressive symptoms in terms of sociodemographic characteristics and scores of the SIS and the EQ-5D VAS. Multiple linear regression models were calculated to investigate the association between PSD and subjective health status and HRQOL. Three months after the stroke, 17.8% of patients had depressive symptoms. Patients with PSD showed significantly worse SIS and EQ-5D VAS scores. In addition, an independent negative linear association between PSD and subjective health status and between PSD and all domains of SIS could be found. The study confirmed that PSD is common in patients with mild stroke and negatively related to all stroke-specific HRQOL domains. The results underline the importance of early screening for PSD in stroke patients since it may hinder a successful rehabilitation.

ZusammenfassungIm Rahmen der Prä-GIT-Studie sollen Informationen zur Prävalenz und zum Verlauf von präkanzerösen und frühmalignen Läsionen im oberen Gastrointestinaltrakt (OGIT) gewonnen sowie Hochrisikogruppen identifiziert werden. Studienteilnehmer erhalten im Rahmen einer regulären Vorsorgekoloskopie nach vorangegangener Einverständniserklärung in derselben Sitzung eine standardisierte hochauflösende Gastroskopie. Für die Hauptphase der Studie ist geplant, 5000 Teilnehmer in 30 gastroenterologischen Praxen in Bayern einzuschließen. Zur Vorbereitung wurde diese Pilotstudie durchgeführt, um die Machbarkeit des Studienprotokolls, die Akzeptanz der Untersuchung sowie die Durchführung in der „Praxis“-Realität zu prüfen. Methodik Drei gastroenterologische Praxen in Bayern nahmen an der dreimonatigen Pilotphase von 10/2018 bis 12/2018 teil. Nach entsprechender Aufklärung wurde Patienten, die sich zur Vorsorgekoloskopie in diesen Praxen vorstellten, zusätzlich eine diagnostische Gastroskopie angeboten. Die Gastroskopien erfolgten nach einer vorgegebenen Arbeitsanweisung (Standard Operating Procedure, SOP). Zusätzlich erfolgten eine Datenerhebung zu Ernährung und Lebensstil anhand eines Selbstausfüllfragebogens sowie die Sammlung von Bioproben. Ergebnisse Innerhalb von 3 Monaten wurden 52 Probanden in drei Praxen in Bayern in die Studie eingeschlossen. Das durchschnittliche Alter lag bei 63,4 Jahren. Die durchschnittliche Untersuchungszeit lag bei 11 Minuten, Komplikationen traten keine auf. Ein Teilnehmer zeigte einen Polyp im Bereich des Recessus piriformis, 21 Teilnehmer zeigten eine Refluxösophagitis, vier Teilnehmer einen Barrett-Ösophagus, davon einer histologisch einen Barrett-Ösophagus mit LGIEN, ein Teilnehmer wies einen Ösophaguspolyp mit leichtgradiger Plattenepitheldysplasie auf, 12 Teilnehmer eine mit Helicobacter pylori assoziierte Gastritis. Eine korpusdominante Atrophie wurde in einem Fall und ein Duodenal-Adenom mit LGIEN in zwei Fällen beschrieben. 100 % bzw. 89 % der Teilnehmer stellten eine Blut- bzw. eine Stuhlprobe für weitere Untersuchungen zur Verfügung. Alle Teilnehmer füllten zudem den Patientenfragebogen aus. Zusammenfassung Durch die Prä-GIT-Studie soll erstmals für Deutschland eine solide Datenbasis generiert werden, um die Häufigkeiten verschiedener prämaligner und frühkanzeröser Veränderungen im oberen Gastrointestinaltrakt valide schätzen zu können. Die jetzige Pilotphase liefert wichtige Erkenntnisse zur Machbarkeit sowie zur Verbesserung der Prozesse im Rahmen der Hauptphase der Studie. Erfreulicherweise zeigte sich eine sehr große Akzeptanz der Teilnahme an der Studie.

Purpose Diet is one of the most important modifiable risk factors for the development of type 2 diabetes. Here, we aim to identify dietary patterns and to investigate their association with prediabetes, undetected diabetes and prevalent diabetes. Methods The present study included 1305 participants of the cross-sectional population-based KORA FF4 study. Oral glucose tolerance test (OGTT) measurements together with a physician-confirmed diagnosis allowed for an accurate categorization of the participants according to their glucose tolerance status into normal glucose tolerance (n = 698), prediabetes (n = 459), undetected diabetes (n = 49), and prevalent diabetes (n = 99). Dietary patterns were identified through principal component analysis followed by hierarchical clustering. The association between dietary patterns and glucose tolerance status was investigated using multinomial logistic regression models. Results A Prudent pattern, characterized by high consumption of vegetables, fruits, wholegrains and dairy products, and a Western pattern, characterized by high consumption of red and processed meat, alcoholic beverages, refined grains and sugar-sweetened beverages, were identified. Participants following the Western pattern had significantly higher chances of having prediabetes (odds ratio [OR] 1.92; 95% confidence interval [CI] 1.35, 2.73), undetected diabetes (OR 10.12; 95% CI 4.19, 24.43) or prevalent diabetes (OR 3.51; 95% CI 1.85, 6.67), compared to participants following the Prudent pattern. Conclusion To our knowledge, the present study is one of the few investigating the association between dietary patterns and prediabetes or undetected diabetes. The use of a reference group exclusively including participants with normal glucose tolerance might explain the strong associations observed in our study. These results suggest a very important role of dietary habits in the prevention of prediabetes and type 2 diabetes.

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.

Background: The Nutrition Societies of Germany, Austria, and Switzerland as the joint editors of the “D-A-CH reference values for nutrient intake” have revised the reference values for vitamin B6 in summer 2019. Summary: For women, the average requirement (AR) for vitamin B6 intake was derived on the basis of balance studies using a pyridoxal-5′-phosphate (PLP) plasma concentration of ≥30 nmol/L as a biomarker of an adequate vitamin B6 status. The recommended intake (RI) was derived considering a coefficient of variation of 10%. The RIs of vitamin B6 for men, children, and adolescents were extrapolated from the vitamin B6 requirement for women considering differences in body weight, an allometric exponent, growth factors as appropriate, and a coefficient of variation. For infants aged 0 to under 4 months, an estimated value was set based on the vitamin B6 intake via breast feeding. The reference value for infants aged 4 to under 12 months was extrapolated from the estimated value for infants under 4 months of age and the average vitamin B6 requirement for adults. The reference values for pregnant and lactating women consider the requirements for the foetus and the loss via breast milk. Key Messages: According to the combined analysis of 5 balance studies, the AR for vitamin B6 to ensure a plasma PLP concentration of ≥30 nmol/L is 1.2 mg/day for adult females and the extrapolated AR for adult males is 1.3 mg/day. The corresponding RIs of vitamin B6 are 1.4 mg/day for adult females and 1.6 mg/day for adult males, independent of age. For infants, the estimated value is 0.1 mg/day and 0.3 mg/day, depending on age. The AR of vitamin B6 for children and adolescents ranges between 0.5 and 1.5 mg/day, and the RI is between 0.6 mg/day and 1.6 mg/day. During pregnancy, the AR is 1.3 mg/day in the first trimester and 1.5 mg/day in the second and third trimesters; the RI is 1.5 mg/day in the first trimester and 1.8 mg/day in the second and third trimesters. For lactating women, the AR is 1.3 mg/day and the RI is 1.6 mg/day.

SCOPE: It is unclear which factors influence the inter-individual variations of postprandial changes in blood glucose. Therefore, we investigated whether the habitual diet is associated with the postprandial glycemic response. METHODS AND RESULTS: Clinical and metabolic data from healthy adults (young adults with 18-25 years, middle-aged adults with 40-65 years, and older adults with 75-85 years) at baseline and during an oral glucose tolerance test (OGTT) was collected. Habitual diet was assessed by a food frequency questionnaire and two 24-hour food lists. Regression models were fitted to examine associations between habitual diet and glucose incremental area under the curve (iAUCmin ). The intake of cereals and cereal products is negatively associated with glucose iAUCmin (p = 0.002) in the total cohort (N = 459, 50% women, 55±21 years, BMI 26±5kg/m2 ). Total carbohydrate intake and the intake of cereals and cereal products predict glucose iAUCmin in the total cohort. Up to 9% of the variance in the glycemic response was explained by the respective dietary parameters identified in the models of the specific age groups. CONCLUSION: These findings suggest, that there are age-specific diet-related effects on postprandial glucose response. Of all investigated dietary parameters, the usual intake of cereals and cereal products seems to play a greater role in postprandial glucose metabolism in more than one age group. Further research is needed, to establish how diet can be optimized based on age and the postprandial response. This article is protected by copyright. All rights reserved.

Previous studies on the association between proton pump inhibitor (PPI) intake and the increased risk of dementia has shown discrepancies in their conclusions. We aimed to provide updated evidence based on extensive bias assessments and quantitative sensitivity analyses.We searched the databases PubMed, EMBASE, SCOPUS, CENTRAL and clinicaltrials.gov for prospective studies that examined an association between PPI use and dementia, up to February 2022. Each study was assessed using the Cochrane risk of bias assessment tools for non-randomized studies of interventions (ROBINS-I) or randomized trials (RoB2). Pooled risk ratios (RRs) and 95% prediction intervals were computed using random-effects models. Sensitivity analyses were adjusted for small-study bias.We included nine observational studies with 204 108 dementia cases in the primary analysis on the association between PPI use vs. non-use and dementia, and the RR was 1.16 (95% CI = 1.00; 1.35). After adjusting for small-study bias by Copas selection model and Rücker's shrinkage procedure, the RR was 1.16 (1.02; 1.32) and 1.15 (1.13; 1.17), respectively. A subgroup analysis of PPI use vs. non-use regarding Alzheimer's disease risk yielded an RR of 1.15 (0.89; 1.50). The secondary analysis on the risk of dementia by use of PPI vs. histamine-2 receptor antagonist showed an RR of 1.03 (0.66; 1.62).This meta-analysis provided no clear evidence for an association between PPI intake and the risk of dementia. Due to discrepancies in sensitivity analyses, however, some risk of dementia by PPI use cannot be ruled out. Since an unequivocal conclusion is still pending, further research is warranted.

Background: The aim of this study was to examine the predictive value of specific changes in admission ECG on long-term outcome in acute myocardial infarction (AMI). Methods: From 2000 until 2017 all AMI cases (n = 9,689) in the study area of Augsburg, Germany, were prospectively recorded. For this study, all patients with a first-time AMI, who survived the first 28 days, were considered. Median observational time was 6.7 years (IQR: 3.6–10.9). Each case was assigned to one of the following groups according to the admission ECG: ‘ST-segment elevation’, ‘ST-segment depression’, ‘T-wave inversion’, ‘unspecific changes’, ‘normal ECG’ and ‘bundle branch block’ (BBB). Multivariable adjusted COX regression models were calculated to compare long-term all-cause mortality. Results: The final regression model revealed a significantly higher mortality among patients with BBB (HR: 1.52 [1.34–1.73], p-value: < 0.001) and ‘ST-segment depression’ (HR: 1.16 [1.03–1.29], p-value: 0.01252) compared to the STEMI group (reference group). The ‘normal ECG’ group (HR: 0.76 [0.66–0.87], p-value: < 0.001) on the other hand was associated with significantly lower long-term mortality. The ‘T-wave inversion’ group (HR: 1.08 [0.96–1.21]) and the ‘unspecific changes’ group (HR: 1.05 [0.94–1.17]) did not differ significantly from the STEMI group. Conclusion: ST-segment depressions and BBB admission ECGs go along with higher long-term mortality in AMI patients compared to STEMI cases. This should be taken into account by physicians when treating patients with NSTEMIs. Only the complete absence of AMI-related ECG changes predicts a more favorable outcome.

Evidence suggests that people react differently to the same diet due to inter-individual differences. However, few studies have investigated variation in response to dietary interventions based on individuals' baseline metabolic characteristics. This study aims to examine the differential reaction of metabotype subgroups to an OGTT and a dietary fiber intervention.We assigned 356 healthy participants of an OGTT sub-study and a 12-week dietary fiber intervention sub-study within the enable cluster to three metabotype subgroups previously identified in the KORA F4 study population. To explore the association between plasma glucose level and metabotype subgroups, we used linear mixed models adjusted for age, sex, and physical activity. Individuals in different metabotype subgroups showed differential responses to OGTT. Compared to the healthy metabotype (metabotype 1), participants in intermediate metabotype (metabotype 2) and unfavorable metabotype (metabotype 3) had significantly higher plasma glucose concentrations at 120 min after glucose bolus (β = 7.881, p = 0.005; β = 32.79, p 0.001, respectively). Additionally, the linear regression model showed that the Area under the curve (AUC) of plasma glucose concentrations was significantly different across the metabotype subgroups. The associations between metabotype subgroups and metabolic parameters among fiber intervention participants remained insignificant in the multivariate-adjusted linear model. However, the metabotype 3 had the highest mean reduction in insulin, cholesterol parameters (TC, LDLc, and non-HDLc), and systolic and diastolic blood pressure at the end of the intervention period.This study supports the use of the metabotype concept to identify metabolically similar subgroups and to develop targeted dietary interventions at the metabotype subgroup level for the primary prevention of diet-related diseases.

BackgroundPost-stroke fatigue is a common symptom after stroke. However, studies on the factors associated with early and late fatigue are scarce. The objective of this study was to identify variables associated with early and late fatigue.MethodsIn the German Stroke Cohort Augsburg (SCHANA) study, participants were interviewed during their hospital stay and completed a postal questionnaire 3 and 12 months post-stroke. Fatigue was assessed using the Fatigue Assessement Scale (FAS). In addition, depression was measured by the Patient Health Questionnaire (PHQ-9), general health status by the EQ-5D visual analog scale, and physical activity by the International Physical Activity Questionnaire (IPAQ). Multivariable regression models were used to determine the associations between FAS scores at 3 and 12 months post-stroke and demographic, psychosocial and health-related covariables.ResultsAmong 505 participants, the frequency of fatigue was 31.1% 3 months and 29.1% 12 months post-stroke. Prior stroke (ß = 2.37, p = 0.0076), prior diagnosis of depression (ß = 5.04, p = 0.0001), higher NIHSS (ß = 0.25, p = 0.0360) and higher PHQ-9 scores (ß = 0.55, p < 0.0001) were significantly associated with higher fatigue levels 3 months post-stroke. Additionally, younger age (ß = −0.07, p = 0.0219), a worse rating of general health at baseline (ß = −0.04, p = 0.0287) and low pre-stroke physical activity (ß = −0.0004, p = 0.0089) were significantly associated with higher fatigue levels 12 months after stroke.ConclusionsFatigue is a common and persisting symptom even in patients with mild impairment. Prior depressive disorder and early depressive symptoms were the most relevant predictors of both early and late fatigue.

Iron-related disorders of the liver can result in serious health conditions, such as liver cirrhosis. Evidence on the role of modifiable lifestyle factors like nutrition in liver iron storage is lacking. Thus, we aimed to assess the association of habitual diet with liver iron content (LIC). We investigated 303 participants from the population-based KORA-MRI study who underwent whole-body magnetic resonance imaging (MRI). Dietary habits were evaluated using repeated 24 h food lists and a food frequency questionnaire. Sex-stratified multiple linear regression models were applied to quantify the association between nutrition variables of interest and LIC, adjusting for liver fat content (LFC), energy intake, and age. Mean age of participants was 56.4 ± 9.0 years and 44.2% were female. Mean LIC was 1.23 ± 0.12 mg/g dry weight, with higher values in men than in women (1.26 ± 0.13 and 1.20 ± 0.10 mg/g, p < 0.001). Alcohol intake was positively associated with LIC (men: β = 1.94; women: β = 4.98, p-values < 0.03). Significant negative associations with LIC were found for fiber (β = −5.61, p < 0.001) and potassium (β = −0.058, p = 0.034) for female participants only. Furthermore, LIC was highly correlated with liver fat content in both sexes. Our findings suggests that there are sex-specific associations of habitual dietary intake and LIC. Alcohol, fiber, and potassium may play a considerable role in liver iron metabolism.

Excessive fat accumulation in adipose tissue depots and organs such as the pancreas and the liver is associated with systemic low-grade chronic inflammation.To investigate the association between abdominal, hepatic, and pancreatic fat and the circulating level of inflammatory biomarkers.We used data from a subsample of the Study of Health in Pomerania (SHIP-Trend, n = 469). The plasma concentration of 37 inflammatory biomarkers was measured using the Bio-Plex-Pro™-Human-Inflammation-Panel-1. Subcutaneous and visceral adipose tissue (SAT and VAT), as well as hepatic and pancreatic fat, were determined by magnetic resonance imaging. We assessed the associations between fat content and inflammatory biomarkers using multiple linear regression.Hepatic fat was associated with MMP-2 (β -0.11), PTX3 (β -0.14), and TNFSF12 (β -0.06). Pancreatic fat was associated with sTNFR1 (β 0.15), sTNFR2 (β 0.11), and sCD163 (β 0.13). VAT and SAT were associated with sCD163 (βOur findings provide new insights into the involvement of hepatic and pancreatic fat on systemic inflammation.

Purpose: Both low levels of vitamin D and of physical activity are associated with all-cause, cancer, and cardiovascular disease mortality. There is some evidence based on self-reported activity levels that physically more active individuals have higher vitamin D serum levels. The aim was to investigate associations between objectively measured and self-reported physical activity, respectively, and vitamin D serum concentrations in the US population. Methods: Data from NHANES 2003-2006 (n=6,370, aged ≥18years) were analyzed using multiple regression analyses. A total of 6,370 individuals aged 18years and older with valid data on vitamin D serum levels and physical activity were included. Objective physical activity was assessed using accelerometers; self-reported physical activity was based on the NHANES physical activity questionnaire. Results: An increase of 10min of objectively measured and self-reported moderate-to-vigorous activities per day was associated with an increase in circulating vitamin D of 0.32ng/ml (95% CI 0.17, 0.48) and of 0.18ng/ml (95% CI 0.12, 0.23), respectively. The odds ratio for being vitamin D deficient (

Simple Summary The causal impact of body fat distribution on female-specific cancers is largely unknown. For the first time we used a two-sample multivariable Mendelian randomization (MR) approach to elucidate the role and causal relations of body composition assessed by segmental bioelectrical impedance analysis on the risks of breast, endometrial and ovarian cancers and their subtypes. We found that abdominal fat content increases the risk for ovarian cancer and its endometrioid and clear cell subtypes independent of overall fat content. General adiposity has a protective effect on risk of breast cancer and its ER- and ER+ subtypes but increases the risk for endometrial cancer, ovarian cancer, and the endometrioid ovarian cancer subtype. This study extends the literature by addressing specifically the causal role of visceral fat on female-specific cancers. Abstract Background: Mounting evidence shows that adiposity increases female-specific cancer risk, but the role of body fat distribution is less clear. We used a two-sample Mendelian randomization (MR) approach to elucidate causal relations of body fat distribution to the risks of breast, endometrial and ovarian cancers and their subtypes. Methods: Body composition was assessed using segmental bioelectrical impedance analysis, yielding trunk, arm, and leg fat ratios (TFR, AFR, LFR) and BMI including 195,043 and 434,794 European women, respectively. The sample sizes for the outcomes ranged between 58,396 and 228,951. Causal effects were estimated per one standard deviation increment in the respective exposure within the radial regression framework. Robust sensitivity analyses were performed to verify MR assumptions. In a multivariable MR setting, the proportion of risk attributable to overall and abdominal fat content was assessed. Results: TFR, which represents abdominal fat content, was associated with ovarian cancer and its clear cell and endometrioid histotypes independent of overall fat content. BMI was inversely associated with breast cancer and its ER− and ER+ subtypes, but positively with endometrial cancer and ovarian cancer, including its endometrioid histotype. These estimates were confirmed using AFR as proxy for overall body fat. Conclusions: Visceral adiposity seems to be a driver of elevated ovarian cancer risk, particularly of the endometrioid and clear cell ovarian cancer histotypes. General adiposity decreases the risk of breast cancer but increases the risk of endometrial and ovarian cancer.

BACKGROUND: Associations between increased dietary fat and decreased carbohydrate intake with circulating HDL and non-HDL cholesterol have not been conclusively determined. OBJECTIVE: We assessed these relations in 8 European observational human studies participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) using harmonized data. METHODS: Dietary macronutrient intake was recorded using study-specific dietary assessment tools. Main outcome measures were lipoprotein cholesterol concentrations: HDL cholesterol (mg/dL) and non-HDL cholesterol (mg/dL). A cross-sectional analysis on 5919 participants (54% female) aged 13-80 y was undertaken using the statistical platform DataSHIELD that allows remote/federated nondisclosive analysis of individual-level data. Generalized linear models (GLM) were fitted to assess associations between replacing 5% of energy from carbohydrates with equivalent energy from total fats, SFAs, MUFAs, or PUFAs with circulating HDL cholesterol and non-HDL cholesterol. GLM were adjusted for study source, age, sex, smoking status, alcohol intake and BMI. RESULTS: The replacement of 5% of energy from carbohydrates with total fats or MUFAs was statistically significantly associated with 0.67mg/dL (95% CI: 0.40, 0.94) or 0.99mg/dL (95% CI: 0.37, 1.60) higher HDL cholesterol, respectively, but not with non-HDL cholesterol concentrations. The replacement of 5% of energy from carbohydrates with SFAs or PUFAs was not associated with HDL cholesterol, but SFAs were statistically significantly associated with 1.94mg/dL (95% CI: 0.08, 3.79) higher non-HDL cholesterol, and PUFAs with -3.91mg/dL (95% CI: -6.98, -0.84) lower non-HDL cholesterol concentrations. A statistically significant interaction by sex for the association of replacing carbohydrates with MUFAs and non-HDL cholesterol was observed, showing a statistically significant inverse association in males and no statistically significant association in females. We observed no statistically significant interaction by age. CONCLUSIONS: The replacement of dietary carbohydrates with fats had favorable effects on lipoprotein cholesterol concentrations in European adolescents and adults when fats were consumed as MUFAs or PUFAs but not as SFAs.

Effective policies to address poor food choices and dietary patterns need to consider the complex set of motives affecting eating behavior. This study examined how different eating motives are associated with anthropometry, body composition, and dietary intake. Our analysis is based on a cross-sectional sample with 429 healthy adults in three different age groups collected in Germany from 2016 to 2018. Dietary intake, Body Mass Index (BMI), waist circumference (WC), and fat-free mass (FFM) were measured by standardized methods. Eating motives were measured using The Eating Motivation Scale (TEMS). Regressing dietary intakes and anthropometric indicators on TEMS motives, we identify the main sources of variation in diet and nutritional status separately for men and women. Results indicated the Health motive to be positively associated with FFM (B±SE=1.72±0.44) and negatively with WC (B±SE=-3.23±0.81) for men. For women, the Need & Hunger motive was positively associated with FFM (B±SE=1.63±0.44) and negatively with WC (B±SE=-2.46±0.81). While Liking and Habits were the most frequently stated eating motives, we did not find them to be significantly related to the nutritional status. Other motives were associated with dietary intake but not anthropometry or body composition. The Price motive was positively and the Convenience motive was negatively associated with energy (B±SE=63.77±19.98;B±SE=-46.96±17.12) and carbohydrate intake (B±SE=7.15±2.65;B±SE=-5.98±2.27) for men. The results highlight the need for more differentiated analyses of eating motives, beyond comparing the relative importance of motives based on mean values, towards the association of motives with dietary intake and nutritional status.

Animal sterols, plant sterols and bile acids in stool samples have been suggested as biomarkers of dietary intake. It is still unknown whether they also reflect long-term habitual dietary intake and can be used in aetiological research. In a subgroup of the Cooperative Health Research in the Augsburg Region (KORA FF4) study, habitual dietary intake was estimated based on repeated 24-h food list and a FFQ. Stool samples were collected according to a standard operating procedure and those meeting the quality criteria were extracted and analysed by means of a metabolomics technique. The present study is based on data from 513 men and 495 women with a mean age of 60 and 58 years, respectively, for which faecal animal and plant sterols and bile acids concentrations and dietary intake data were available. In adjusted regression models, the associations between food intake and log-normalised metabolite concentrations were analysed. Bonferroni correction was used to account for multiple testing. In this population-based sample, associations between habitual dietary intake and faecal concentrations of animal sterols were identified, while the impact of usual diet on bile acids was limited. A habitual diet high in ‘fruits’ and ‘nuts and seeds’ is associated with lower animal faecal sterols concentrations, whereas a diet high in ‘meat and meat products’ is positively related to faecal concentrations of animal sterols. A positive association between glycocholate and fruit consumption was found. Further studies are necessary for evaluation of faecal animal sterols as biomarkers of diet. The findings need to be confirmed in other populations with diverse dietary habits.

Background Physical inactivity is an established risk factor for several cancers of the digestive system and female reproductive organs, but the evidence for liver cancers is less conclusive. Methods The aim of this study was to synthesize prospective observational studies on the association of physical activity and liver cancer risk by means of a systematic review and meta-analysis. We searched Medline, Embase, and Scopus from inception to January 2019 for prospective studies investigating the association of physical activity and liver cancer risk. We calculated mean hazard ratios (HRs) and 95% confidence intervals (CIs) using a random-effects model. We quantified the extent to which an unmeasured confounder or an unaccounted selection variable could shift the mean hazard ratio to the null. Results Fourteen prospective studies, including 6,440 liver cancers, were included in the systematic review and meta-analysis. The mean hazard ratio for high compared with low physical activity was 0.75 (95% CI = 0.63 to 0.89; 95% prediction interval = 0.52 to 1.07; I² = 64.2%). We estimated that 67.6% (95% CI = 56.6% to 78.5%) of all true effect estimates would have a hazard ratio less than 0.8. Bias analysis suggested than an unobserved confounder would have to be associated with a 1.99-fold increase in the risk of physical activity or liver cancer to explain away the observed mean hazard ratio. An unaccounted for selection variable would have to be related to exposure and endpoint with a relative risk of 1.58 to explain away the mean hazard ratio. Conclusions Physical activity is inversely related to the risk of liver cancer. Further studies with objectively measured physical activity and quasi-experimental designs addressing confounding are needed.