Comorbidities and advanced stage diagnosis (ASD) are both associated with poorer cancer outcomes, but the association between comorbidities and ASD is poorly understood. We summarized epidemiological ...evidence on the association between comorbidities and ASD of selected cancers in a systematic review and meta-analysis. We searched PubMed and Web of Science databases up to June 3rd, 2021 for studies assessing the association between comorbidities and ASD of lung, breast, colorectal, or prostate cancer. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random-effects models. Also, potential variations in the associations between comorbidities and ASD by cancer type were investigated using random-effects meta-regression. Thirty-seven studies were included in this review, including 8,069,397 lung, breast, colorectal, and prostate cancer patients overall. The Charlson comorbidity index score was positively associated with ASD (stages III–IV) of breast cancer but was inversely associated with ASD of lung cancer (pinteraction = 0.004). Regarding specific comorbidities, diabetes was positively associated with ASD (OR = 1.17, 95%CI = 1.09–1.26), whereas myocardial infarction was inversely associated with ASD (OR = 0.84, 95%CI = 0.75–0.95). The association between renal disease and ASD differed by cancer type (pinteraction < 0.001). A positive association was found with prostate cancer (OR = 2.02, 95%CI = 1.58–2.59) and an inverse association with colorectal cancer (OR = 0.84, 95%CI = 0.70–1.00). In summary, certain comorbidities (e.g., diabetes) may be positively associated with ASD of several cancer types. It needs to be clarified whether closer monitoring for early cancer signs or screening in these patients is reasonable, considering the problem of over-diagnosis particularly relevant in patients with short remaining life expectancy such as those with comorbidities. Also, evaluation of the cost-benefit relationship of cancer screening according to the type and severity of comorbidity (rather than summary scores) may be beneficial for personalized cancer screening in populations with chronic diseases.
•The association between comorbidity and advanced stage diagnosis (ASD) depends on the type of cancer and comorbidity.•Certain comorbidities (e.g., diabetes) are positively associated with ASD.•It needs to be clarified whether closer monitoring for early signs or screening in these patients is reasonable.•Evaluation of the benefit of screening according to the type of comorbidity may be beneficial for personalized screening.
Studies indicate that dietary fat quantity and quality influence the gut microbiota composition which may as a consequence impact metabolic health. This systematic review aims to summarize the ...results of available studies in humans on dietary fat intake (quantity and quality), the intestinal microbiota composition and related cardiometabolic health outcomes.
We performed a systematic review (CRD42018088685) following PRISMA guidelines and searched for literature in Medline, EMBASE, and Cochrane databases.
From 796 records, 765 records were excluded based on title or abstract. After screening of 31 full-text articles six randomized controlled trials (RCT) and nine cross-sectional observational studies were included. Our results of interventional trials do not suggest strong effects of different amounts and types of dietary fat on the intestinal microbiota composition or on metabolic health outcomes while observational studies indicate associations with the microbiota and health outcomes. High intake of fat and saturated fatty acids (SFA) may negatively affect microbiota richness and diversity and diets high in monounsaturated fatty acids (MUFA) may decrease total bacterial numbers whereas dietary polyunsaturated fatty acids (PUFA) had no effect on richness and diversity.
High fat and high SFA diets can exert unfavorable effects on the gut microbiota and are associated with an unhealthy metabolic state. Also high MUFA diets may negatively affect gut microbiota whereas PUFA do not seem to negatively affect the gut microbiota or metabolic health outcomes. However, data are not consistent and most RCT and observational studies showed risks of bias.
With declining response proportions in population-based research the importance of evaluating the effectiveness of measures aimed at improving response increases. We investigated whether an ...additional flyer with information about the study influences participation in a follow-up questionnaire and the time participants take to send back filled questionnaire.
In a trial embedded within the German National Cohort we compared responses to invitations for a follow-up questionnaire either including a flyer with information about the cohort study or not including it. Outcomes of interest were participation in the follow-up (yes vs. no) and time to response (in days). We analyzed paradata from baseline recruitment to account for differences in recruitment history between participants.
Adding a flyer to invitations did neither influence the likelihood of participation in the follow-up (OR 0.94, 95% CI: 0.80, 1.11), nor the time it took participants to return completed questionnaires (β̂ = 1.71, 95% CI: - 1.01, 4.44). Subjects who, at baseline, needed to be reminded before eventually participating in examinations and subjects who scheduled three or more appointments until eventually completing baseline examinations were less likely to complete the follow-up questionnaire and, if they did, took more time to complete questionnaires.
Evaluating the effectiveness of measures aimed at increasing response can help to improve the allocation of usually limited resources. Characteristics of baseline recruitment can influence response to follow-up studies and therefore information about recruitment history (i.e., paradata) might prove useful to tailor follow-up recruitments to those who were difficult to recruit during baseline. To this end, however, it is necessary to routinely and meticulously collect paradata during recruitment.
Prior to implementing gene expression analyses from blood to a larger cohort study, an evaluation to set up a reliable and reproducible method is mandatory but challenging due to the specific ...characteristics of the samples as well as their collection methods. In this pilot study we optimized a combination of blood sampling and RNA isolation methods and present reproducible gene expression results from human blood samples.
The established PAXgeneTM blood collection method (Qiagen) was compared with the more recent TempusTM collection and storing system. RNA from blood samples collected by both systems was extracted on columns with the corresponding Norgen and PAX RNA extraction Kits. RNA quantity and quality was compared photometrically, with Ribogreen and by Real-Time PCR analyses of various reference genes (PPIA, β-ACTIN and TUBULIN) and exemplary of SIGLEC-7.
Combining different sampling methods and extraction kits caused strong variations in gene expression. The use of PAXgeneTM and TempusTM collection systems resulted in RNA of good quality and quantity for the respective RNA isolation system. No large inter-donor variations could be detected for both systems. However, it was not possible to extract sufficient RNA of good quality with the PAXgeneTM RNA extraction system from samples collected by TempusTM collection tubes. Comparing only the Norgen RNA extraction methods, RNA from blood collected either by the TempusTM or PAXgeneTM collection system delivered sufficient amount and quality of RNA, but the TempusTM collection delivered higher RNA concentration compared to the PAXTM collection system. The established Pre-analytix PAXgeneTM RNA extraction system together with the PAXgeneTM blood collection system showed lowest CT-values, i.e. highest RNA concentration of good quality. Expression levels of all tested genes were stable and reproducible.
This study confirms that it is not possible to mix or change sampling or extraction strategies during the same study because of large variations of RNA yield and expression levels.
Background:
Chemotherapy is an established treatment for stage III colon cancer cases. Older age is known to be associated with less chemotherapy use in these patients, but there might be other ...relevant factors besides age that influence treatment administration. We summarized evidence on associations between comorbidity and adjuvant chemotherapy administration in stage III colon cancer patients in a systematic review and meta-analysis.
Methods:
We searched the PubMed and Web of Science databases up to 2 June 2020 for studies on comorbidities and chemotherapy use in patients with stage III colon cancer. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using random-effects models. Subgroup analyses according to year of colon cancer diagnosis, timing of comorbidity assessment, and geographical region were also conducted.
Results:
Thirty-three studies were included in this review, including 219,406 stage III colon cancer patients overall. Chemotherapy administration was 60.9% (95% CI: 56.9% to 64.9%), increasing from 57.1% before 2001 to 66.3% after 2010. There were inverse associations between comorbidities and chemotherapy administration. Compared with patients with Charlson comorbidity score 0, those with scores 1 (OR = 0.79, 95% CI = 0.72–0.87) and 2+ (OR = 0.49, 95% CI = 0.42–0.56) received chemotherapy less often. Among comorbidities, the strongest predictors of chemotherapy non-use were dementia (OR = 0.37, 95% CI = 0.33–0.54), followed by heart failure (OR = 0.44, 95% CI = 0.28–0.70) and stroke (OR = 0.56, 95% CI = 0.38–0.81).
Conclusions:
Merely 60% of stage III colon cancer patients receive chemotherapy. Comorbidities are strong predictors of chemotherapy non-use, but the association differs by comorbid condition and is strongest with dementia. Given the survival disadvantage of colon cancer patients with comorbidities, further evidence on the risk–benefit ratio of chemotherapy according to the type and severity of comorbidity and on the extent to which the survival disadvantage of comorbidity is explained by less use or lower tolerability of chemotherapy is needed to foster personalized medical care in these patients.
We determined the prevalence of anti-nuclear autoantibodies (ANAs) in the German adult population and examined the association between ANAs and cardiovascular and metabolic disorders.
We used data ...and blood samples from the pretest phases of the German National Cohort, obtained from six of the 18 study centers (n = 1199). All centers applied standardized instruments including face-to-face interviews, anthropometric measurements and collection of blood samples. Self-reported histories of diabetes mellitus, heart attack and elevated blood cholesterol and/or lipids were recorded. Height, weight and blood pressure were measured. ANAs were detected using a semi-automated system (AKLIDES®; Medipan GmbH, Dahlewitz, Germany). A positive ANA was defined as a titer ≥ 1:80. ANA were classified as weakly (1:80 or 1:160), moderately (1:320 or 1:640) or strongly (≥1:1280) positive. Specific autoantibodies against nuclear antigens were detected with second-step assays according to the ANA staining pattern. Associations between the assessed disorders and ANA positivity and pattern were examined using sex and age-adjusted mixed-effects logistic regression models.
Thirty-three percent (95% confidence interval; 31-36%) of the 1196 participants (measurements could not be obtained from three samples) were ANA positive (titer ≥ 1:80). The proportions of weakly, moderately and strongly positive ANA were 29%, 3.3% and 1.3%, respectively. ANA positivity was more common among women than men across all titers (χ
, p = 0.03). ANA positivity, even when stratified according to height of titer or immunofluorescent pattern, was not associated with diabetes, elevated blood cholesterol and/or lipids, obesity or hypertension. Second-step autoantibody assays were positive in 41 of the 83 samples (49%) tested, with anti-DFS70 (n = 13) and anti-dsDNA (n = 7) being most frequent. These subgroups were too small to test for associations with the disorders assessed.
The prevalence of ANA positivity in the German general population was similar to values reported from other countries. Contrary to other studies, there was no association with selected self-reported and objectively measured cardiovascular and metabolic variables.
We conducted a trial embedded within the German National Cohort comparing the responses to study invitations sent in recycled envelopes of grey color vs. envelopes of white color. We analyzed ...paradata for reactions to the invitation letters by potential subjects, the duration between mailing date of the invitation and active responses, and study participation.
Grey envelopes only slightly increased the chance of active responses (OR 1.16, 95% CI 0.83, 1.62) to the invitation letter. Potential study subjects with German nationality (OR 3.75, 95% CI 2.07, 7.66) and age groups above 50 years (50-59: OR 1.78, 95% CI 1.19, 2.69; 60-69: OR 2.25, 95% CI 1.48, 3.43) were more likely to actively respond to the invitation letter. The duration between mailing date of the invitation and active response was not associated with envelope color, sex, nationality, or age. Our trial replicates previous observations that the color of the envelope of a study invitation does not influence the likelihood of an active response or study participation.
Nearly 10 years ago, the World Health Organization reported the increasing prevalence of overweight and obesity worldwide as a challenge for public health due to the associated adverse consequences. ...Epidemiological studies established a firm relationship between an elevated body mass index and chronic conditions such as diabetes, dyslipidemia, hypertension, heart disease, non-alcoholic fatty liver disease, and some types of cancer. Omic studies demonstrated that microRNA (miRNA) profile changes in tissues correlate with a number of diseases, including obesity. Recent studies showed a remarkable stability of miRNAs also in blood, emphasizing their potential as theranostic agents for a variety of disorders and conditions. A number of miRNAs enriched in homeostasis of obesity and metabolic disorders have been characterized in previous researches.
This work was finalized to investigate the differential circulating miRNAs signature in early childhood obesity. Our cross-sectional study analyzed the signature of circulating miRNAs in plasma samples of normal weight (
= 159) and overweight/obese (
= 149) children and adolescents participating to the I.Family study, an EC-funded study finalized to investigate the etiology of overweight, obesity and related disorders and the determinants of food choice, lifestyle, and related health outcomes in children and adolescents of eight European countries (www.ifamilystudy.eu).
Differences in miRNA signature with respect to anthropometric and biochemical variables were analyzed. A high degree of variability in levels of circulating miRNAs was identified among children from different countries, in line with recent reports supporting the hypothesis that these molecules are likewise affected by environmental and lifestyle factors. A panel of miRNAs differentially expressed in overweight/low-grade obesity children was characterized (miR-551a and miR-501-5p resulted upregulated; miR-10b-5p, miR-191-3p, miR-215-5p, and miR-874-3p resulted downregulated). ROC curves were also constructed for experimentally confirmed miRNAs. Single miRNAs generally exhibited low AUC values with the highest values for miR-874-3p and miR-501-5p which in combination provided an interesting value (AUC = 0.782). Pearson's analysis confirmed that miR-10b-5p, miR-215-5p, miR-501-5p, miR-551a, and miR-874-3p significantly correlated with BMI
-score. Molecular interactions of obesity-associated miRNAs were also predicted by bioinformatics tools.
Our work showed that several circulating miRNAs are differentially represented in overweight/low-grade obesity children and adolescents. Although causal pathways cannot be firmly inferred, it is conceivable that circulating miRNAs may be new biomarkers of early childhood obesity.
ISRCTN, ISRCTN62310987. Registered 23/02/2018 - Retrospectively registered.
Zusammenfassung
Hintergrund
Mit Beginn der SARS-CoV-2-Pandemie und der nachfolgenden Maßnahmen zu ihrer Eindämmung im Frühjahr 2020 ist rasch die Frage nach Auswirkungen der Beschränkung sozialer ...Kontakte auf die psychische Gesundheit der Bevölkerung aufgekommen. Einsamkeit beschreibt eine wahrgenommene Qualität der eigenen Kontakte und Beziehungen zu anderen Menschen. Zahlreiche Studien haben einen Zusammenhang von Einsamkeit mit somatischen und psychischen Erkrankungen aufgezeigt.
Ziel
Auswertung der Häufigkeit von Einsamkeit und ihrer Beziehung zu Angst- und Depressionssymptomen in der ersten Welle der Pandemie im Mai 2020.
Methoden
Zwischen 2014 und 2019 hat die NAKO-Gesundheitsstudie 205.000 Personen im Alter zwischen 20 und 69 Jahren in 18 Studienzentren in Deutschland rekrutiert und untersucht. Die nachfolgende Zweituntersuchung musste aufgrund der Pandemie im Frühjahr 2020 unterbrochen werden. In dieser Zeit wurde ein COVID-19-bezogener Fragebogen entwickelt und an alle Teilnehmenden verschickt. Ausgewertet wurden die 113.928 Fragebögen, die innerhalb der ersten 30 Tage zurückgeschickt wurden. Einsamkeit wurde mit der 3‑Item UCLA Loneliness Scale, Angst und Depression mit den PHQ-9- und GAD-7-Skalen des Patient Health Questionnaire erhoben.
Ergebnisse
Im Mai 2020 nahmen sich 31,7 % der NAKO-Teilnehmenden als einsam wahr. Frauen und junge Menschen waren häufiger als Männer und ältere Personen betroffen. Mit steigender Wahrnehmung von Einsamkeit nahm der Schweregrad von Depressions- und Angstsymptomen stetig zu. Einsame Personen während der Pandemie hatten bereits zur NAKO-Basisuntersuchung mehr depressive und Angstsymptome angegeben als NAKO-Teilnehmende, die sich in der Pandemie nicht einsam fühlten.
Schlussfolgerung
In der NAKO-Gesundheitsstudie zeigte sich während der ersten Phase der Pandemie eine Zunahme von Einsamkeit und ihr deutlicher Zusammenhang mit schlechterer, psychischer Gesundheit.
We examined acceptability, preference and feasibility of collecting nasal and oropharyngeal swabs, followed by microbiome analysis, in a population-based study with 524 participants. Anterior nasal ...and oropharyngeal swabs were collected by certified personnel. In addition, participants self-collected nasal swabs at home four weeks later. Four swab types were compared regarding (1) participants' satisfaction and acceptance and (2) detection of microbial community structures based on deep sequencing of the 16 S rRNA gene V1-V2 variable regions. All swabbing methods were highly accepted. Microbial community structure analysis revealed 846 phylotypes, 46 of which were unique to oropharynx and 164 unique to nares. The calcium alginate tipped swab was found unsuitable for microbiome determinations. Among the remaining three swab types, there were no differences in oropharyngeal microbiomes detected and only marginal differences in nasal microbiomes. Microbial community structures did not differ between staff-collected and self-collected nasal swabs. These results suggest (1) that nasal and oropharyngeal swabbing are highly feasible methods for human population-based studies that include the characterization of microbial community structures in these important ecological niches, and (2) that self-collection of nasal swabs at home can be used to reduce cost and resources needed, particularly when serial measurements are to be taken.
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