Large-scale assessment of physical activity in a population using high-resolution hip-worn accelerometry: the German National Cohort (NAKO).

Large population-based cohort studies utilizing device-based measures of physical activity are crucial to close important research gaps regarding the potential protective effects of physical activity on chronic diseases. The present study details the quality control processes and the derivation of physical activity metrics from 100 Hz accelerometer data collected in the German National Cohort (NAKO). During the 2014 to 2019 baseline assessment, a subsample of NAKO participants wore a triaxial ActiGraph accelerometer on their right hip for seven consecutive days. Auto-calibration, signal feature calculations including Euclidean Norm Minus One (ENMO) and Mean Amplitude Deviation (MAD), identification of non-wear time, and imputation, were conducted using the R package GGIR version 2.10-3. A total of 73,334 participants contributed data for accelerometry analysis, of whom 63,236 provided valid data. The average ENMO was 11.7 ± 3.7 mg (milli gravitational acceleration) and the average MAD was 19.9 ± 6.1 mg. Notably, acceleration summary metrics were higher in men than women and diminished with increasing age. Work generated in the present study will facilitate harmonized analysis, reproducibility, and utilization of NAKO accelerometry data. The NAKO accelerometry dataset represents a valuable asset for physical activity research and will be accessible through a specified application process.

Sustainable diets and risk of overweight and obesity: A systematic review and meta-analysis.

Sustainable diets are gaining interest as a possible approach to tackle climate change and the global extent of obesity. Yet, the association between sustainable diets and adiposity remains unclear. We performed a systematic review and meta-analysis, calculating summary relative risks and 95% confidence intervals (CI). We pooled maximally adjusted risk estimates, assessed heterogeneity and publication bias, calculated the E-value, and evaluated the risk of bias across the included studies. A total of eight studies were eligible for analysis. Comparing the highest versus the lowest levels of adherence to sustainable diets, the pooled effect estimate was 0.69 (95% CI = 0.62-0.76) for overweight and 0.61 (95% CI = 0.47-0.78) for obesity. These results suggest that sustainable diets may decrease the risk of overweight/obesity and therefore could serve as enablers for improving both public and planetary health. An agreed-upon clear definition of sustainable diets would enhance the comparability of future studies in this area.

Differences in Anthropometric Measures Based on Sex, Age, and Health Status: Findings From the German National Cohort (NAKO).

BACKGROUND: Obesity is a worldwide health problem. We conducted detailed analyses of anthropometric measures in a comprehensive, population-based, current cohort in Germany. METHODS: In the German National Cohort (NAKO), we analyzed cross-sectional data on body-mass index (BMI), waist and hip circumference, subcutaneous (SAT) and visceral adipose tissue (VAT) as measured by ultrasound, and body fat percentage. The data were stratified by sex, age, and self-reported physicians' diagnoses of cardiovascular diseases (CVD), metabolic diseases (MetD), cardiometabolic diseases (CMD), and cancer. RESULTS: Data were available from 204 751 participants (age, 49.9 ± 12.8 years; 50.5% women). Body size measures generally increased with age. Men had a higher BMI, larger waist circumference, and more VAT than women, while women had a larger hip circumference, more SAT, and a higher body fat percentage than men. For example, the mean BMI of participants over age 60 was 28.3 kg/m2 in men and 27.6 kg/m2 in women. CVD, MetD, and CMD were associated with higher anthropometric values, while cancer was not. For example, the mean BMI was 25.3 kg/m2 in healthy women, 29.4 kg/m2 in women with CMD, and 25.4 kg/m2 in women with cancer. CONCLUSION: Obesity is widespread in Germany, with notable differences between the sexes in anthropometric values. Obesity was more common in older participants and those with chronic diseases other than cancer. Elevated values were especially common in multimorbid individuals.

Calcium intake in vegan and vegetarian diets: A systematic review and Meta-analysis.

In recent years, plant-based diets have experienced increasing popularity. However, plant-based diets may not always ensure an adequate supply of micronutrients, in particular calcium. We performed a systematic review and meta-analysis of calcium intake in vegan and vegetarian diets as compared to omnivorous diets. We searched PubMed and Web of Science and identified 2,009 potentially relevant articles. Mean calcium intake values were pooled and standardized mean differences (SMD) and 95% confidence intervals (CI) were computed.We analyzed 74 studies, including 7,356 vegan, 51,940 vegetarian, and 107,581 omnivorous participants. Of these, dietary calcium intake was examined in 23 studies of vegans, 60 studies of vegetarians and 74 studies of omnivores. Vegans showed a substantially lower calcium intake than vegetarians (SMD = -0.57; 95%CI = -0.83 to -0.32; p = <0.0001) and omnivores (SMD = -0.70; 95%CI = -0.95 to -0.59; p < 0.0001), whereas no statistically significant difference in calcium intake was noted between vegetarians and omnivores (SMD = 0.07; 95%CI = -0.04 to 0.19; p = 0.1976). In conclusion, vegans show a lower calcium intake than vegetarians and omnivores. This finding emphasizes the need for vegans to monitor their calcium status.

Association between circadian physical activity patterns and mortality in the UK Biobank.

BACKGROUND: The benefit of physical activity (PA) for increasing longevity is well-established, however, the impact of diurnal timing of PA on mortality remains poorly understood. We aimed to derive circadian PA patterns and investigate their associations with all-cause mortality. METHODS: We used 24 h PA time series from 96,351 UK Biobank participants aged between 42 and 79 years at accelerometry in 2013-2015. Functional principal component analysis (fPCA) was applied to obtain circadian PA patterns. Using multivariable Cox proportional hazard models, we related the loading scores of these fPCs to estimate risk of mortality. RESULTS: During 6.9 years of follow-up, 2,850 deaths occurred. Four distinct fPCs accounted for 96% of the variation of the accelerometry data. Using a loading score of zero (i.e., average overall PA during the day) as the reference, a fPC1 score of + 2 (high overall PA) was inversely associated with mortality (Hazard ratio, HR = 0.91; 95% CI: 0.84-0.99), whereas a score of -2 (low overall PA) was associated with higher mortality (1.69; 95% CI: 1.57-1.81; p for non-linearity < 0.001). Significant inverse linear associations with mortality were observed for engaging in midday PA instead of early and late PA (fPC3) (HR for a 1-unit increase 0.88; 95% CI: 0.83-0.93). In contrast, midday and nocturnal PA instead of early and evening PA (fPC4) were positively associated with mortality (HR for a 1-unit increase 1.16; 95% CI: 1.08-1.25). CONCLUSION: Our results suggest that it is less important during which daytime hours one is active but rather, to engage in some level of elevated PA for longevity.

Effect of 25-hydroxyvitamin D levels on the internalising dimension as a transdiagnostic risk factor: Mendelian randomisation study.

BACKGROUND: Observational studies indicate a relationship between vitamin D (25-hydroxyvitamin D; 25OHD) deficiency and the development of internalising disorders, especially depression. However, causal inference approaches (e.g. Mendelian randomisation) did not confirm this relationship. Findings from biobehavioural research suggests that new insights are revealed when focusing on psychopathological dimensions rather than on clinical diagnoses. This study provides further evidence on the relationship between 25OHD and the internalising dimension. AIMS: This investigation aimed at examining the causality between 25OHD and internalising disorders including a common internalising factor. METHOD: We performed a two-sample Mendelian randomisation using genome-wide association study (GWAS) summary data for 25OHD (417 580 participants), major depressive disorder (45 591 cases; 97 674 controls), anxiety (5580 cases; 11 730 controls), post-traumatic stress disorder (12 080 cases; 33 446 controls), panic disorder (2248 cases; 7992 controls), obsessive-compulsive disorder (2688 cases; 7037 controls) and anorexia nervosa (16 992 cases; 55 525 controls). GWAS results of the internalising phenotypes were combined to a common factor representing the internalising dimension. We performed several complementary analyses to reduce the risk of pleiotropy and used a second 25OHD GWAS for replication. RESULTS: We found no causal relationship between 25OHD and any of the internalising phenotypes studied, nor with the common internalising factor. Several pleiotropy-robust methods corroborated the null association. CONCLUSIONS: Following current transdiagnostic approaches to investigate mental disorders, our results focused on the shared genetic basis between different internalising phenotypes and provide no evidence for an effect of 25OHD on the internalising dimension.

Health-Promoting and Sustainable Behavior in University Students in Germany: A Cross-Sectional Study.

Health-promoting and sustainable behaviors, such as active transportation and sustainable diets, are associated with positive effects on human health and the environment. In order to unlock the potential of university students as key actors and multipliers, it is of interest to investigate their level of knowledge about the health effects of climate change and their willingness toward and implementation of health-promoting and sustainable behaviors. In November 2021, an online survey was conducted among students at the University of Regensburg, Germany. A total of 3756 participants (response rate 18%; mean age 23 years; 69% women) provided valid data. A large proportion of medical students (48%) considered themselves well-informed about the health-related effects of climate change, while only a small proportion (22%) of students within economic/computer/data sciences and law felt informed. Most participants knew about the impact of climate change on malnutrition (78%), but considerably fewer were aware of its impact on cardiovascular diseases (52%). Participants who considered themselves informed were consistently more willing to engage in climate-friendly behavior, and this willingness was also reflected in their actions, as they simultaneously promoted a healthy lifestyle. Across all academic disciplines, there is a strong need for knowledge transfer regarding topics that combine health and sustainable development.

Relationship between genetically proxied vitamin D and psoriasis risk: a Mendelian randomization study.

BACKGROUND: Observational research suggests that vitamin D levels affect psoriasis. However, observational studies are prone to potential confounding or reverse causation, which complicates interpreting the data and drawing causal conclusions. AIM: To apply Mendelian randomization (MR) methods to comprehensively assess a potential association between vitamin D and psoriasis. METHODS: Genetic variants strongly associated with 25-hydroxyvitamin D (25OHD) in genome-wide association study (GWAS) data from 417 580 and 79 366 individuals from two independent studies served as instrumental variables (used as the discovery and replication datasets, respectively). As the outcome variable, we used GWAS data of psoriasis (13 229 people in the case group, 21 543 in the control group). We used (i) biologically validated genetic instruments, and (ii) polygenic genetic instruments to assess the relationship between genetically proxied vitamin D and psoriasis. We carried out inverse-variance weighted (IVW) MR analyses for the primary analysis. In sensitivity analyses, we used robust MR approaches. RESULTS: MR analyses of both the discovery and replication datasets did not show an effect of 25OHD on psoriasis. Neither the IVW MR analysis of the biologically validated instruments [discovery dataset: odds ratio (OR) 0.99; 95% confidence interval (CI) 0.88-1.12, P = 0.873; replication dataset: OR 0.98, 95% CI 0.66-1.46, P = 0.930] nor that of the polygenic genetic instruments (discovery dataset: OR 1.00, 95% CI 0.81-1.22, P = 0.973; replication dataset: OR 0.94, 95% CI 0.64-1.38, P = 0.737) revealed an impact of 25OHD on psoriasis. CONCLUSION: The present MR study did not support the hypothesis that vitamin D levels, measured by 25OHD, affect psoriasis. This study was conducted on Europeans, so the conclusions may not be applicable to all ethnicities.

Suicide Mortality Risk among Patients with Lung Cancer-A Systematic Review and Meta-Analysis.

The risk for suicide in patients with cancer is higher compared to the general population. However, little is known about patients with lung cancer specifically. We therefore implemented a systematic review and random-effects meta-analysis of retrospective cohort studies on suicide in patients with lung cancer. We searched a high number of common databases up to 02/2021. For the systematic review, a total of 23 studies was included. To exclude bias due to patient sample overlap, the meta-analysis was performed on 12 studies. The pooled standardized mortality ratio (SMR) for suicide was 2.95 (95% Confidence Interval (CI) = 2.42-3.60) for patients with lung cancer as compared to the general population. Subgroups with a pronouncedly higher risk for suicide compared to the general population were found for patients living in the USA (SMR = 4.17, 95% CI = 3.88-4.48), with tumors of late stage (SMR = 4.68, 95% CI = 1.28-17.14), and within one year after diagnosis (SMR = 5.00, 95% CI = 4.11-6.08). An increased risk for suicide was found in patients with lung cancer, with subgroups at particular risk. Patients at increased risk should be monitored more closely for suicidality and should receive specialized psycho-oncological and psychiatric care. Further studies should clarify the role of smoking and depressive symptoms on suicidality among lung cancer patients.

Targeted therapies in patients with newly diagnosed glioblastoma-A systematic meta-analysis of randomized clinical trials.

Glioblastoma (GB) is the most common malignant primary brain tumor in adults. The standard of care for newly diagnosed GB involves surgical resection followed by radiochemotherapy with temozolomide, with or without tumor-treating fields. In recent years, various efforts have been made to identify suitable molecularly targeted treatment options for malignant brain tumors. This meta-analysis provides an overview of recently published randomized controlled trials (RCTs) with and without molecular stratification, analyzing targeted agents in patients with newly diagnosed GB. The Cochrane Library, MEDLINE (Ovid), ClinicalTrials.gov, WHO's International Clinical Trials Registry Platform, and Google Scholar were searched for RCTs on targeted therapies in patients with newly diagnosed glioblastoma. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were extracted and pooled in a random-effects meta-analysis. Twelve RCTs (n = 3941 patients) involving protein kinase inhibitors, proteasome and histone deacetylase inhibitors, anti-angiogenic approaches and poly (ADP-ribose) polymerase (PARP) inhibitors were included in the meta-analysis. None of the targeted agents achieved a significant benefit with regard to OS (HR = 0.98 [95% confidence interval (CI) 0.86-1.11, P = .7731]). By comparison, targeted therapy showed a benefit for PFS (HR = 0.83 [95% CI 0.74-0.94, P = .0037]), especially for patients with an unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter (0.75 [95% CI 0.56-0.99, P = .0440]). Prolongation of PFS was largely driven by VEGF inhibition with bevacizumab (HR = 0.70 [95% CI 0.61-0.80, P = .0000]). VEGF inhibition with bevacizumab prolonged PFS in patients with newly diagnosed glioblastoma compared to standard care. However, no improvement in OS was observed with any of the targeted agents.

COVID-19-related deaths: a 2-year inter-wave comparison of mortality data from Germany.

PURPOSE: The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has caused substantial mortality worldwide. We investigated clinical and demographic features of COVID-19-related deaths that occurred between March 2020 and January 2022 in Regensburg, Germany. METHODS: We compared data across four consecutive time periods: March 2020 to September 2020 (period 1), October 2020 to February 2021 (period 2), March 2021 to August 2021 (period 3), and September 2021 to January 2022 (period 4). RESULTS: Overall, 405 deaths in relation to COVID-19 were reported. The raw case fatality ratio (CFR) was 0.92. In periods 1 to 4, the CFRs were 1.70%, 2.67%, 1.06%, and 0.36%. The age-specific CFR and mortality were highest in persons aged ≥ 80 years in period 2 while mortality in younger cases increased with time. The median age at death was 84 years and it varied slightly across periods. Around 50% of cases of death were previously hospitalized. In all time periods, the cause of death was mostly attributed to COVID-19. Over the four periods, we did not find significant changes in the distribution of sex and risk factors for severe disease. The most frequent risk factor was cardio-circulatory disease. CONCLUSION: In conclusion, the CFR decreased over time, most prominently for period 4. Mortality was considerable and younger cases were increasingly at risk.

Antimicrobial drug use and the risk of glioma: A case-control study.

BACKGROUND: The use of antibiotics has been associated with increased risks of various cancers. Comprehensive information on the association of antibiotic use with the risk of glioma is lacking. METHODS: We performed a large case-control study based on the Clinical Practice Research Datalink (CPRD) GOLD from the United Kingdom. We identified 4423 glioma cases recorded between 1995 and 2020 and matched them to controls (1:10) on the date of diagnosis (i.e., the index date), age, sex, general practice, and number of years of medical history in the database prior to the index date. We conducted conditional logistic regression analyses to calculate odds ratios (ORs) with 95% confidence intervals (CIs). The exposures of interest were the use of antimicrobial drugs, including antibacterial, antiviral, antifungal, antiprotozoal, and anthelmintic drugs with specific subclasses, where possible. RESULTS: We found no substantially increased risk of glioma after ever-use of antibiotics (OR 1.13, 95% CI 1.03-1.24). The risk did not increase with the increasing number of prescriptions received or with increasing time from first use to cancer diagnosis. The use of polyenes was associated with a weakly decreased risk of glioma (OR 0.81, 95% CI 0.67-0.96).

Longitudinal associations of sedentary behavior and physical activity with body composition in colorectal cancer survivors up to 2 years post treatment.

PURPOSE: We investigated longitudinal associations of sedentary behavior, light-intensity physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) with body composition in colorectal cancer (CRC) survivors, between 6 weeks and 24 months post treatment. In addition, we explored whether body composition mediated associations of sedentary behavior and MVPA with fatigue. METHODS: A prospective cohort study was conducted in 459 stage I-III CRC patients recruited at diagnosis. Measurements were performed of accelerometer-assessed sedentary time (hours/day), self-reported LPA and MVPA (hours/week), anthropometric assessment of body mass index (BMI), waist circumference and fat percentage (measures of adiposity), and muscle circumference and handgrip strength (measures of muscle mass/function) repeated at 6 weeks, and 6, 12 and 24 months post treatment. Longitudinal associations of sedentary time and physical activity with body composition were analyzed using confounder-adjusted linear mixed models. Mediation analyses were performed to explore the role of body mass index (BMI) and handgrip strength as mediators in associations of sedentary time and MVPA with fatigue. RESULTS: Less sedentary time and LPA were, independent of MVPA, longitudinally associated with increased handgrip strength, but not with measures of adiposity. More MVPA was associated with increased adiposity and increased handgrip strength. Higher BMI partly mediated associations between higher sedentary time and more fatigue. CONCLUSION: Within the first two years after CRC treatment, changes in sedentary behavior, physical activity and body composition are interrelated and associated with fatigue. Intervention studies are warranted to investigate causality. TRIAL REGISTRATION: The EnCoRe study is registered at trialregister.nl as NL6904 (former ID: NTR7099).

Longitudinal associations of plasma metabolites with persistent fatigue among colorectal cancer survivors up to 2 years after treatment.

The underlying biological mechanisms causing persistent fatigue complaints after colorectal cancer treatment need further investigation. We investigated longitudinal associations of circulating concentrations of 138 metabolites with total fatigue and subdomains of fatigue between 6 weeks and 2 years after colorectal cancer treatment. Among stage I-III colorectal cancer survivors (n = 252), blood samples were obtained at 6 weeks, and 6, 12 and 24 months posttreatment. Total fatigue and fatigue subdomains were measured using a validated questionnaire. Tandem mass spectrometry was applied to measure metabolite concentrations (BIOCRATES AbsoluteIDQp180 kit). Confounder-adjusted longitudinal associations were analyzed using linear mixed models, with false discovery rate (FDR) correction. We assessed interindividual (between-participant differences) and intraindividual longitudinal associations (within-participant changes over time). In the overall longitudinal analysis, statistically significant associations were observed for 12, 32, 17 and three metabolites with total fatigue and the subscales "fatigue severity," "reduced motivation" and "reduced activity," respectively. Specifically, higher concentrations of several amino acids, lysophosphatidylcholines, diacylphosphatidylcholines, acyl-alkylphosphatidylcholines and sphingomyelins were associated with less fatigue, while higher concentrations of acylcarnitines were associated with more fatigue. For "fatigue severity," associations appeared mainly driven by intraindividual associations, while for "reduced motivation" stronger interindividual associations were found. We observed longitudinal associations of several metabolites with total fatigue and fatigue subscales, and that intraindividual changes in metabolites over time were associated with fatigue severity. These findings point toward inflammation and an impaired energy metabolism due to mitochondrial dysfunction as underlying mechanisms. Mechanistic studies are necessary to determine whether these metabolites could be targets for intervention.

Body shape phenotypes of multiple anthropometric traits and cancer risk: a multi-national cohort study.

BACKGROUND: Classical anthropometric traits may fail to fully represent the relationship of weight, adiposity, and height with cancer risk. We investigated the associations of body shape phenotypes with the risk of overall and site-specific cancers. METHODS: We derived four distinct body shape phenotypes from principal component (PC) analysis on height, weight, body mass index (BMI), waist (WC) and hip circumferences (HC), and waist-to-hip ratio (WHR). The study included 340,152 men and women from 9 European countries, aged mostly 35-65 years at recruitment (1990-2000) in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After a median follow-up of 15.3 years, 47,110 incident cancer cases were recorded. PC1 (overall adiposity) was positively associated with the risk of overall cancer, with a HR per 1 standard deviation (SD) increment equal to 1.07 (95% confidence interval 1.05 to 1.08). Positive associations were observed with 10 cancer types, with HRs (per 1 SD) ranging from 1.36 (1.30-1.42) for endometrial cancer to 1.08 (1.03-1.13) for rectal cancer. PC2 (tall stature with low WHR) was positively associated with the risk of overall cancer (1.03; 1.02-1.04) and five cancer types which were not associated with PC1. PC3 (tall stature with high WHR) was positively associated with the risk of overall cancer (1.04; 1.03-1.05) and 12 cancer types. PC4 (high BMI and weight with low WC and HC) was not associated with overall risk of cancer (1.00; 0.99-1.01). CONCLUSIONS: In this multi-national study, distinct body shape phenotypes were positively associated with the incidence of 17 different cancers and overall cancer.

Sedentary behavior and cancer-an umbrella review and meta-analysis.

Several systematic reviews and meta-analyses have summarized the association between sedentary behavior (SB) and cancer. However, the level of evidence and the potential for risk of bias remains unclear. This umbrella review summarized the current data on SB in relation to cancer incidence and mortality, with a particular emphasis on assessing the risk of bias. We searched PubMed, Web of Science and Cochrane Database for systematic reviews and meta-analyses on the association between SB and cancer incidence and mortality. We also searched for recent observational studies not yet included in existing meta-analyses. We re-calculated summary risk estimates for cancer incidence and mortality using random effects models. We included 14 meta-analyses covering 17 different cancer sites from 77 original studies. We found that high SB levels increase the risk for developing ovarian, endometrial, colon, breast, prostate, and rectal cancers, with relative risks of 1.29 (95% confidence interval (CI) = 1.08-1.56), 1.29 (95% CI = 1.16-1.45), 1.25 (95% CI = 1.16-1.33), 1.08 (95% CI = 1.04-1.11), 1.08 (95% CI = 1.00-1.17), and 1.07 (95% CI = 1.01-1.12), respectively. Also, we found an increased risk of cancer mortality of 1.18 (95% CI = 1.09-1.26). Most associations between SB and specific cancer sites were supported by a "suggestive" level of evidence. High levels of SB are associated with increased risk of several types of cancer and increased cancer mortality risk.

Relationship between periodontitis and psoriasis: A two-sample Mendelian randomization study.

AIM: Observational research suggests that periodontitis affects psoriasis. However, observational studies are prone to reverse causation and confounding, which hampers drawing causal conclusions and the effect direction. We applied the Mendelian randomization (MR) method to comprehensively assess the potential bi-directional association between periodontitis and psoriasis. MATERIALS AND METHODS: We used genetic instruments from the largest available genome-wide association study of European descent for periodontitis (17,353 cases, 28,210 controls) to investigate the relationship with psoriasis (13,229 cases, 21,543 controls), and vice versa. Causal Analysis Using Summary Effect (CAUSE) estimates and inverse variance-weighted (IVW) MR analyses were used for the primary analysis. Robust MR approaches were used for sensitivity analyses. RESULTS: Both univariable methods, CAUSE and IVW MR analyses, did not reveal any impact of periodontitis on psoriasis (CAUSE odds ratio [OR] = 1.00, p = 1.00; IVW OR = 1.02, p = .6247), or vice versa (CAUSE OR = 1.01, p = .5135; IVW OR = 1.00, p = .7070). The null association was corroborated by pleiotropy-robust methods with ORs close to 1 and p-values >.59. Overall, MR analyses did not suggest any effect of periodontitis on psoriasis. Similarly, there was no evidence to support an effect of psoriasis on periodontitis. CONCLUSIONS: Within the limitations of this MR study, the outcomes supported neither periodontitis affecting psoriasis nor psoriasis affecting periodontitis.