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Background: Artificial intelligence (AI) has numerous applications in pathology, supporting diagnosis and prognostication in cancer. However, most AI models are trained on highly selected data, typically one tissue slide per patient. In reality, especially for large surgical resection specimens, dozens of slides can be available for each patient. Manually sorting and labelling whole‐slide images (WSIs) is a very time‐consuming process, hindering the direct application of AI on the collected tissue samples from large cohorts. In this study we addressed this issue by developing a deep‐learning (DL)‐based method for automatic curation of large pathology datasets with several slides per patient. Methods: We collected multiple large multicentric datasets of colorectal cancer histopathological slides from the United Kingdom (FOXTROT, N = 21,384 slides; CR07, N = 7985 slides) and Germany (DACHS, N = 3606 slides). These datasets contained multiple types of tissue slides, including bowel resection specimens, endoscopic biopsies, lymph node resections, immunohistochemistry‐stained slides, and tissue microarrays. We developed, trained, and tested a deep convolutional neural network model to predict the type of slide from the slide overview (thumbnail) image. The primary statistical endpoint was the macro‐averaged area under the receiver operating curve (AUROCs) for detection of the type of slide. Results: In the primary dataset (FOXTROT), with an AUROC of 0.995 [95% confidence interval [CI]: 0.994–0.996] the algorithm achieved a high classification performance and was able to accurately predict the type of slide from the thumbnail image alone. In the two external test cohorts (CR07, DACHS) AUROCs of 0.982 [95% CI: 0.979–0.985] and 0.875 [95% CI: 0.864–0.887] were observed, which indicates the generalizability of the trained model on unseen datasets. With a confidence threshold of 0.95, the model reached an accuracy of 94.6% (7331 classified cases) in CR07 and 85.1% (2752 classified cases) for the DACHS cohort. Conclusion: Our findings show that using the low‐resolution thumbnail image is sufficient to accurately classify the type of slide in digital pathology. This can support researchers to make the vast resource of existing pathology archives accessible to modern AI models with only minimal manual annotations. [ABSTRACT FROM AUTHOR]

A study conducted in Germany analyzed the impact of the COVID-19 pandemic on the diagnosis of colorectal cancer (CRC). The study found that there were significant delays in CRC diagnoses during the first two years of the pandemic, resulting in a lower number of cases than expected. The largest discrepancy was observed in the second quarter of 2020. Although case numbers seemed to return to expected values in the later quarters of 2021, there is still a need to address the sustained delay in diagnoses. These findings are consistent with previous reports on the impact of the pandemic on CRC diagnoses and treatment in Germany. Efforts should be made to minimize such delays in the future. [Extracted from the article]

This article discusses the use of fecal immunochemical tests (FITs) for hemoglobin in colorectal cancer (CRC) screening. The study found that higher fecal hemoglobin concentrations were associated with a higher prevalence of advanced neoplasia (AN) in participants undergoing screening colonoscopy in Germany. This suggests that risk stratification based on fecal hemoglobin concentration could be useful in determining appropriate screening intervals. The given text provides data on the prevalence of negative and positive COVID-19 test results among different age groups and genders. The data shows that the majority of individuals tested negative for COVID-19, with higher percentages of negative results among men compared to women. The data also indicates that the likelihood of testing positive for COVID-19 increases with age. However, the reasons for these differences in test results among different groups are not provided. Another document presents the results of a study on the diagnostic accuracy of fecal immunochemical tests (FIT) for detecting advanced neoplasia (CRC or advanced adenoma) in colorectal cancer (CRC) screening. The study found that at a cutoff of 17 µg/g, the positivity rate was 9.9%, sensitivity and positive predictive value were 39%, and specificity and negative predictive value were 93%. The study suggests that individuals with higher negative FIT values are at a higher risk for CRC and may benefit from personalized screening intervals. However, the study has limitations and further research is needed. [Extracted from the article]

We explored the relationship between benefit finding (BF)/posttraumatic growth (PTG) at baseline and health-related quality of life (HRQOL) at baseline and follow-up in long-term cancer survivors (LTCS; ≥5-year post-diagnosis). HRQOL was assessed in LTCS in 2009–2011 (5- to 16-year post-diagnosis, baseline) and re-assessed in 2018/2019 (14- to 24-year post-diagnosis, follow-up). BF and PTG were measured at baseline; mean scores were dichotomized into 'none-to-low' (<3) and 'moderate-to-high' (> =3). Linear regression models and linear mixed regression models were employed to assess the association of BF/PTG with HRQOL. Of the 6057 baseline participants, 4373 were alive in 2019, of whom 2704 completed the follow-up questionnaire. Cross-sectionally, LTCS with none-to-low BF reported better HRQOL at baseline and at follow-up than LTCS with higher BF. Longitudinally, no difference was found between none-to-low and moderate-to-high BF on the HRQOL change from baseline to follow-up. HRQOL differences between the PTG groups were not statistically significant cross-sectionally and longitudinally, except those participants with moderate-to-high PTG reported higher role functioning and global health status/QOL. Cross-sectionally, BF was significantly negatively related to subscales of HRQOL, while PTG was positively correlated to role functioning and global health status/QOL. The results add further evidence that BF and PTG are two different positive psychological concepts. [ABSTRACT FROM AUTHOR]

Background: This study aimed to describe the characteristics and mortality of two cohorts of patients with chronic coronary syndrome (CCS) recruited with identical study designs in the same rehabilitation clinics but approximately 10 years apart. Methods: The KAROLA cohorts included patients with CCS participating in an inpatient cardiac rehabilitation programme in Germany (KAROLA-I: years 1999/2000, KAROLA-II: 2009–2011). Blood samples and information on sociodemographic factors, lifestyle, and medical treatment were collected at baseline, at the end of rehabilitation, and after one year of follow-up. A biomarker-based risk model (ABC-CHD model) and Cox regression analysis were used to evaluate cardiovascular (CV) and non-CV mortality risk. Results: We included 1130 patients from KAROLA-I (mean age 58.7 years, 84.4% men) and 860 from KAROLA-II (mean age 60.4 years, 83.4% men). Patients in the KAROLA-I cohort had significantly higher concentrations of CV biomarkers and fewer patients were taking CV medications, except for statins. The biomarker-based ABC-CHD model provided a higher estimate of CV death risk for patients in the KAROLA-I cohort (median 3-year risk, 3.8%) than for patients in the KAROLA-II cohort (median 3-year risk, 2.7%, p-value for difference < 0.001). After 10 years of follow-up, 91 (8.1%) patients in KAROLA-I and 45 (5.2%) in KAROLA-II had died from a CV event. Conclusions: Advances in disease management over the past 20 years may have led to modest improvements in pharmacological treatment during cardiac rehabilitation and long-term outpatient care for patients with CCS. However, modifiable risk factors such as obesity have increased in the more recent cohort and should be targeted to further improve the prognosis of these patients. [ABSTRACT FROM AUTHOR]

Background: In order to utilize polygenic risk scores (PRSs) for Alzheimer's disease (AD) in a meaningful way, influential factors (i.e. training set) and prediction across groups such as APOE e4 (APOE4) genotype as well as associations to dementia-related biomarkers should be explored. Therefore, we examined the association of APOE4 and various PRSs, based on training sets that utilized differing AD definitions, with incident AD and all-cause dementia (ACD) within 17 years, and with levels of phosphorylated tau181 (P-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) in blood. Secondarily, effect modification by APOE4 status and sex was examined. Methods: In this prospective, population-based cohort study and nested case–control study, 9,940 participants in Germany were enrolled between 2000 and 2002 by their general practitioners and followed for up to 17 years. Participants were included in this study if dementia status and genetic data were available. A subsample of participants additionally had measurements of P-tau181, NfL, and GFAP obtained from blood samples. Cox and logistic regression analyses were used to assess the association of genetic risk (APOE genotype and PRSnoAPOE) with incident ACD/AD and log-transformed blood levels of P-tau181, NfL, and GFAP. Results: Five thousand seven hundred sixty-five participants (54% female, aged 50-75years at baseline) were included in this study, of whom 464 received an all-cause dementia diagnosis within 17 years. The PRSs were not more predictive of dementia than APOE4. An APOE4 specific relationship was apparent with PRSs only exhibiting associations to dementia among APOE4 carriers. In the nested case–control study including biomarkers (n = 712), APOE4 status and polygenic risk were significantly associated to levels of GFAP in blood. Conclusions: The use of PRSs may be beneficial for increased precision in risk estimates among APOE4 carriers. While APOE4 may play a crucial etiological role in initial disease processes such as Aβ deposition, the PRS may be an indicator of further disease drivers as well as astrocyte activation. Further research is necessary to confirm these findings, especially the association to GFAP. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) patients often experience fatigue, poor ability to work, and low quality of life (QoL) after therapy. We conducted a prospective study of 147 CRC patients who underwent a three-week in-patient rehabilitation clinic visit in Germany. Patients completed questionnaires at the start of rehabilitation and at regular 3-month intervals for up to a year. We found a strong correlation between fatigue and QoL, and moderate correlations between fatigue and the ability to work, as well as between QoL and the ability to work. Fatigue, QoL, and ability to work improved significantly from the start of rehabilitation to the three-month follow-up, and there was little change afterward in the first year after rehabilitation. In summary, fatigue, QoL, and the ability to work were highly interconnected in CRC patients, and all of them improved from the start of rehabilitation to the 3-month follow-up. Cancer-related fatigue, low quality of life (QoL), and low ability to work are highly prevalent among colorectal cancer (CRC) patients after tumor surgery. We aimed to analyze their intercorrelations and trajectories in the first year after in-patient rehabilitation in the German multicenter MIRANDA cohort study. Recruitment is ongoing, and we included the first 147 CRC patients in this analysis. Participants filled out questionnaires at the beginning of in-patient rehabilitation (baseline) and at 3, 6, 9, and 12 months after the baseline. The EORTC-QLQ-C30-General-Health-Status (GHS)/QoL, the FACIT-F-Fatigue Scale, and the FACIT-F-FWB-ability-to-work items were used to evaluate QoL, fatigue, and ability to work, respectively. The fatigue and QoL scales were highly correlated (r = 0.606). A moderate correlation was observed between the fatigue and ability to work scales (r = 0.487) and between the QoL and ability to work scales (r = 0.455). Compared to the baseline, a statistically significant improvement in the QoL, ability to work, and fatigue scales were observed at the 3-month follow-up (Wilcoxson signed rank test, all p < 0.0001). The three scales plateaued afterward until the 12-month follow-up. In conclusion, fatigue, QoL, and ability to work were highly interrelated, improved quickly during/after in-patient rehabilitation, and did not change much afterward in German CRC patients. [ABSTRACT FROM AUTHOR]

Background: To assess the prevalence of obesity, obesity-related binge eating, non-obesity-related binge eating, and night eating in five- to six-year-old children and to examine the impact of parental eating disturbances. Methods: When 2020 children attended their obligatory health exam prior to school entry in the city of Aachen, Germany, 1979 parents (97.9%) filled out a questionnaire on their child's eating habits and weight development in a cross-sectional survey. Anthropometric measurements were collected for all children in a standardized form. Results: Episodes of binge eating were found in 2.0% of the children surveyed and night eating in 1.1%. There was a significant relationship between binge eating and obesity but not between night eating and the child's weight. Children's binge eating and night eating were strongly associated with eating disturbances on the part of their mothers (adjusted odds ratios [95% confidence intervals]: 6.1 [2.7-13.5] and 7.8 [2.1-29.4], respectively) and with a non-German native language (adjusted odds ratios [95% confidence intervals]: 2.6 [1.2-5.5] and 11.6 [3.5-38.7], respectively). Conclusions: In concurrence with studies on adulthood, binge eating is linked to obesity already in early childhood. Children of mothers with eating disorders and children of mothers with a non-German native language are at increased risk of developing eating disorders themselves. Future studies should focus on obesity and eating disorders in early childhood; prevention programs should seek to target young children at risk as early as possible.

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19–74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2–3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4–5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies consistently find low concentrations of 25‐hydroxyvitamin D (25(OH)D) in blood to be associated with increased mortality, and a recent large‐scale Mendelian randomization study strongly supports a causal relationship among individuals with low vitamin D status. Evolving evidence suggested that bioavailable or free 25(OH)D may better predict mortality. We aimed to compare the prognostic values of vitamin D–binding protein (VDBP), total, bioavailable, complementary "nonbioavailable", and free 25(OH)D for total and cause‐specific mortality in a large population‐based cohort study of older adults from Germany. Methods: Bioavailable, complementary "nonbioavailable", and free 25(OH)D concentrations were calculated among 5899 participants aged 50–75 years, based on serum concentrations of total 25(OH)D, VDBP, and albumin. The cohort was followed with respect to total and cause‐specific mortality from recruitment in 2001–2002 up to the end of 2018. Multivariable Cox proportional hazards regression models were used to assess the associations between various vitamin D biomarkers and mortality, and further stratified by vitamin D status. Results: During a median follow‐up of 17.1 years, 1739 participants died, of whom 575, 584, and 94 died of cardiovascular diseases, cancer, and respiratory diseases, respectively. Very similar inverse associations with total mortality (hazard ratio (HR) per standard deviation decrease: 1.17, 95% confidence interval (CI): 1.11, 1.24 for total 25(OH)D; HR: 1.14, 95% CI: 1.08, 1.21 for bioavailable 25(OH)D; HR: 1.12, 95% CI: 1.06, 1.18 for free 25(OH)D) and cause‐specific mortalities were seen for all biomarkers of vitamin D status. The strongest associations were consistently seen for respiratory mortality. These inverse associations were strongest among participants with low vitamin D levels (<50 nmol/L). No significant associations were seen between VDBP and mortality. Conclusions: Total, nonbioavailable, bioavailable, and free 25(OH)D showed very similar inverse associations with total and cause‐specific mortality, which were strongest among those with low vitamin D status in this large population‐based cohort. [ABSTRACT FROM AUTHOR]

Background: Parent self‐administered reports are commonly used in studies on childhood atopic dermatitis (AD) but data on its validity are sparse. We aimed to examine the agreement between parent‐ and physician‐reported measures of childhood AD throughout early life and identify the determinants. Methods: In this prospective cohort study, we used data of 449 infants and their mothers recruited in the Ulm SPATZ Health Study in Germany. Longitudinal data of parental and children's caring physicians' reports were used to assess the point and cumulative agreement of parent‐ and physician‐reported AD diagnoses, AD onset age, and trend of agreement at child ages between 1 and 6 years overall and by child and parent demographics and health conditions. A Generalized Estimating Equation model was fitted to identify factors associated with the sensitivity of parent reports. Results: The point agreement between parent‐ and physician‐reported AD was substantial at the age of 1 (kappa = 0.63, 95% CI: 0.51–0.75) but declined with age and became fair after the age of 3 (kappa < 0.40). The cumulative agreement remained moderate at the age of 6 (kappa = 0.51, 95% CI: 0.43–0.60). Parents had a bias towards delayed reporting of the AD onset age. The AD severity was the only strong determinant for the agreement of AD diagnoses and largely explained the variance of the sensitivity of parent reports. Conclusion: The disagreement between parent‐ and physician‐reported AD increases with child age, likely due to the change of AD severity. Using parent‐reported data might miss a substantial portion of mild childhood AD cases. [ABSTRACT FROM AUTHOR]

Simple Summary: Screening for colorectal cancer (CRC) has considerably contributed to declining CRC incidence and mortality rates in Germany over the last two decades. However, evidence on the cost-effectiveness of this public health remains scarce, mostly due to the lack of detailed sex- and age-specific estimates on CRC treatment costs over time. Using a large research database on insurance claims data, we analyzed CRC-related inpatient, outpatient as well as medication costs up to five years after diagnosis and prior to death. Our findings show that costs in the terminal phase of care were consistently on a high level even several years preceding death, mostly driven by high inpatient and medication costs, and substantially higher as compared to the initial phase of care. As well, we observed a consistent pattern of higher costs in men versus women, most markedly in the first year of diagnosis and the final year of life, and strongly varying costs by age. Our findings could be highly useful in informing cost-effectiveness analyses e.g., to further optimize strategies to screen for CRC. Objective: Evidence on the cost-effectiveness of screening for colorectal cancer (CRC) in the German general population remains scarce as key input parameters, the costs to treat CRC, are largely unknown. Here, we provide detailed estimates on CRC treatment costs over time. Methods: Using insurance claims data from the Vilua healthcare research database, we included subjects with newly diagnosed CRC and subjects who died of CRC between 2012 and 2016. We assessed annualized CRC-related inpatient, outpatient and medication costs for up to five years after first diagnosis and prior to death, stratified by sex and age. Findings: We identified 1748 and 1117 subjects with follow-up data for at least 1 year after diagnosis and prior to death, respectively. In those newly diagnosed, average costs were highest in the first year after diagnosis (men, EUR 16,375–16,450; women, EUR 10,071–13,250) and dropped steeply in the following years, with no consistent pattern of differences with respect to age. Costs prior to death were substantially higher as compared to the initial phase of care and consistently on a high level even several years before death, peaking in the final year of life, with strong differences by sex and age (men vs. women, <70 years, EUR 34,351 vs. EUR 31,417; ≥70 years, EUR 14,463 vs. EUR 9930). Conclusion: Once clinically manifest, CRC causes substantial treatment costs over time, particularly in the palliative care setting. Strong differences in treatment costs by sex and age warrant further investigation. [ABSTRACT FROM AUTHOR]

Introduction Subjective cognitive decline (SCD) is an established precursor of dementia. However, the relationship between SCD and dementia has been mostly studied among people aged 65+. We aimed to assess the association between subjective memory difficulties at ages 50–75 with all-cause dementia and dementia-subtypes in a community-based cohort with long-term follow-up. Methods 6,190 individuals (51% female) aged 50–75 years (median age, 62) attending a general health examination (by a total of 684 general practitioners) in Saarland, Germany, in 2000–2002 were recruited for a community-based cohort study. Subjective difficulties regarding short-term and long-term memory were assessed at baseline with two simple yes/no questions. Associations with dementia (−subtypes) diagnoses during 17 years of follow-up were estimated by Cox proportional hazards models. Results 492 participants were diagnosed with dementia during 17 years of follow-up. Participants with short-term memory difficulties were at higher risk to receive incident all-cause dementia and vascular dementia diagnoses both within 0–9 years (age and sex adjusted hazard ratios (aHR), 1.80 and 2.00, respectively) and within 0–17 years (aHR 1.55 and 1.78, respectively) from recruitment (P  < 0.05 in all cases). For clinical Alzheimer's disease, a significant association was only seen within the initial 6 years. There were no associations of long-term memory difficulties with any type of dementia. Conclusions Subjective difficulties in short-term memory predict both intermediate and long-term risk of vascular and all-cause dementia even among late middle-age adults. These results underline the importance of cardiovascular disease prevention efforts well before old age for maintaining cognitive health. [ABSTRACT FROM AUTHOR]

For individuals willing to minimize their lifetime risk of colorectal cancer (CRC), the most effective screening approach remains unclear. Here, we sought to compare the long‐term performance of existing and alternative CRC screening offers in a case study for Germany. Applying the perspective of a perfectly adhering man or woman at average risk, we used COSIMO, a validated Markov‐based multistate model, to simulate the effects of current CRC screening offers in Germany. These include age‐ and sex‐dependent offers for fecal immunochemical testing (FIT) or screening colonoscopy, which may be used twice starting at age 50 in men and age 55 in women. For comparison, we modeled screening colonoscopies at ages 50, 60 and 70, screening colonoscopies at ages 50 and 60, followed by biennial FITs and conventional FIT‐based strategies at varying intervals. We found that the highest reductions in lifetime risks of developing (76%‐84%) and dying from CRC (82%‐90%) were achieved by three colonoscopies, followed by annual FIT screening and strategies combining both modalities. In men, additional screening from age 70 onwards reduced the risk of dying from CRC by another 9% units and resulted in 32 to 39 additional life‐years‐gained per 1000 individuals. Among women, three colonoscopies outperformed current screening offers in all outcomes, at little risk of screening‐related complications. In summary, several FIT‐ and colonoscopy‐based offers yield comparably high CRC risk reductions, including approaches combining both modalities. German screening offers may be optimized by lowering the eligibility age for screening colonoscopy for women, along with additional offers for the elderly. [ABSTRACT FROM AUTHOR]

Purpose: Limited research suggests that cancer survivors have problems with insurance. Our study aimed to gain insight into the proportion of very long-term (14–24 years post-diagnosis) survivors of breast, colorectal, and prostate cancers who had problems with health (HI) and life (LI) insurance. Methods: We used data from CAESAR (CAncEr Survivorship—A multi-Regional population-based study). Participants completed questions on change in insurance providers since cancer diagnosis, problems with requesting (additional) HI or LI, and how potential problems were resolved. We conducted logistic regression to determine factors associated with change in statutory HI. Results: Of the 2714 respondents, 174 (6%) reported having changed HI providers. Most switched between different statutory HI providers (86%), 9% from statutory to private, and 5% from private to statutory. Respondents who changed statutory HI providers were more likely to be prostate cancer survivors (OR 2.79, 95% CI 1.01–7.68) while being ≥ 65 years at time of diagnosis (OR 0.58, 95% CI 0.35–0.96) and having ≥ 2 comorbid conditions (OR 0.61, 95% CI 0.40–0.92) were associated with reduced odds for change. Problems in changing HI were minimal and were resolved with additional contribution. Of the 310 respondents who tried to get LI, 25 respondents reported having difficulties, of whom the majority had their request rejected. Conclusion: Most cancer survivors did not change their HI nor tried to buy LI after cancer diagnosis. Problems with changing statutory HI were generally resolved with additional contribution while the main problem encountered when buying LI was rejection of request. [ABSTRACT FROM AUTHOR]

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Objective To compare the prevalence of potentially inappropriate non-steroidal anti-inflammatory drugs (NSAIDs) among NSAIDs users defined with frequently used potentially inappropriate medication (PIM) lists and to identify the determinants of their use. Design and Setting Cross-sectional survey among community-dwelling older adults from Germany. Subjects N = 284 NSAIDs users aged 65–89 years. Methods All currently regularly or as-needed used drugs were recorded during a home visit. Multivariate logistic regression models were applied to assess the potential determinants of potentially inappropriate NSAIDs use. Results Prevalence of potentially inappropriate NSAIDs use was 54.2%, 45.4%, 29.9%, 20.4%, and 3.5% when applying the STOPP, 2019 Beers, EU(7)-PIM, FORTA, and PRISCUS list, respectively. No study participant was identified as a potentially inappropriate NSAIDs user by all five lists simultaneously. The majority (68%) were identified only by one or two lists. Merely the STOPP and Beers criteria had a moderate inter-instrument agreement. Lower pain severity, gout, peptic ulcer (PU), cardiovascular disease (CVD), and chronic kidney disease (CKD) were statistically significantly associated with potentially inappropriate NSAIDs use defined by the STOPP criteria and the latter three conditions also with the 2019 Beers criteria. Conclusions The STOPP and Beers criteria may be superior to the other lists because they more frequently identify potentially inappropriate NSAIDs use in conditions implying a high risk for NSAIDs' adverse events (i.e. PUD, CKD and CVD). We developed a harmonized, country-independent PIM list for NSAIDs with the same advantages as observed for the STOOP and 2019 Beers criteria and recommended its use. [ABSTRACT FROM AUTHOR]

Background: Cancer studies reported mixed results on benefit finding (BF) and posttraumatic growth (PTG) prevalence and few were focused on long-term survivors.Methods: BF and PTG were assessed in a multi-regional population-based study in Germany with 6952 breast, colorectal and prostate cancer survivors, using the Benefit Finding Scale and Posttraumatic Growth Inventory. We calculated the age-adjusted prevalence, stratified by demographical and clinical characteristics.Results: Overall, 66.0% of cancer survivors indicated moderate-to-high BF, and 20.5% moderate-to-high PTG. Age-adjusted prevalence of BF and PTG differed according to cancer type (breast > colorectal > prostate) and sex (female > male). BF and PTG prevalence were higher in younger than in older respondents; the age-adjusted prevalence was higher in respondents who survived more years after diagnosis. The strength and direction of associations of age-adjusted prevalence with cancer stage, disease recurrence, and time since diagnosis varied according to cancer type and sex.Conclusions: A substantial proportion of long-term cancer survivors reported moderate-to-high BF and PTG. However, the prevalence was lower in older and male cancer survivors, and during the earlier years after cancer diagnosis. Further longitudinal studies on PTG and BF in cancer survivors are warranted to address heterogeneity in survivors' experience after cancer diagnosis. [ABSTRACT FROM AUTHOR]

Background: To understand the potential for early intervention and prevention measures in Alzheimer's disease, the association between risk factors and early pathological change needs to be assessed. Hence, the aim of this study was to determine whether risk factors of Alzheimer's clinical syndrome (clinical AD), such as body mass index (BMI), are associated with Aβ misfolding in blood, a strong risk marker for AD among older adults. Methods: Information on risk factors and blood samples were collected at baseline in the ESTHER study, a population-based cohort study of older adults (age 50–75 years) in Germany. Aβ misfolding in blood plasma was analyzed using an immuno-infrared-sensor in a total of 872 participants in a nested case-control design among incident dementia cases and matched controls. Associations between risk factors and Aβ misfolding were assessed by multiple logistic regression. For comparison, the association between the risk factors and AD incidence during 17 years of follow-up was investigated in parallel among 5987 cohort participants. Results: An inverse association with Aβ misfolding was seen for BMI at age 50 based on reported weight history (aOR 0.64, 95% CI 0.43–0.96, p = 0.03). Similar but not statistically significant associations were seen for BMI at baseline (i.e., mean age 68) and at age 40. No statistically significant associations with Aβ misfolding were found for other risk factors, such as diabetes, smoking, and physical activity. On the other hand, low physical activity was associated with a significantly reduced risk of developing clinical AD compared to physical inactivity. Conclusions: Our results support that AD pathology may be detectable and associated with reduced weight even in middle adulthood, many years before clinical diagnosis of AD. Physical activity might reduce the risk of onset of AD symptoms. [ABSTRACT FROM AUTHOR]

Socioeconomic inequalities in cancer survival have been reported in various countries but it is uncertain to what extent they persist in countries with relatively comprehensive health insurance coverage such as Germany. We investigated the association between area‐based socioeconomic deprivation on municipality level and cancer survival for 25 cancer sites in Germany. We used data from seven population‐based cancer registries (covering 32 million inhabitants). Patients diagnosed in 1998 to 2014 with one of 25 most common cancer sites were included. Area‐based socioeconomic deprivation was assessed using the categorized German Index of Multiple Deprivation (GIMD) on municipality level. We estimated 3‐month, 1‐year, 5‐year and 5‐year conditional on 1‐year age‐standardized relative survival using period approach for 2012 to 2014. Trend analyses were conducted for periods between 2003‐2005 and 2012‐2014. Model‐based period analysis was used to calculate relative excess risks (RER) adjusted for age and stage. In total, 2 333 547 cases were included. For all cancers combined, 5‐year survival rates by GIMD quintile were 61.6% in Q1 (least deprived), 61.2% in Q2, 60.4% in Q3, 59.9% in Q4 and 59.0% in Q5 (most deprived). For most cancer sites, the most deprived quintile had lower 5‐year survival compared to the least deprived quintile even after adjusting for stage (all cancer sites combined, RER 1.16, 95% confidence interval 1.14‐1.19). For some cancer sites, this association was stronger during short‐term follow‐up. Trend analyses showed improved survival from earlier to recent periods but persisting deprivation differences. The underlying reasons for these persisting survival inequalities and strategies to overcome them should be further investigated. What's new? Socioeconomic inequality is known to affect cancer survival rates, even in countries with universal health‐care coverage. This large German study analyzed smaller‐scale population areas (~1200 residents each), and found that survival rates for most common cancers were lower among patients from lower‐income areas than among those from more affluent areas. The underlying causes of this association between socioeconomic deprivation and decreased cancer survival should be further investigated, as should strategies to correct these causal factors. [ABSTRACT FROM AUTHOR]

Inpatient rehabilitation therapy (IRT) is commonly offered to cancer patients during or after cancer treatment in Germany. However, little is known about utilization and long-term effects of this offer in colorectal cancer (CRC) patients. We aimed to assess IRT utilization, determinants of utilization and the association between IRT and survival in CRC patients. CRC patients diagnosed in 2005–2014 recruited in the population-based DACHS study in South West Germany were included. Determinants of IRT utilization were assessed by multivariable logistic regression. Hazard ratios (HRs) of the association of IRT with overall and disease-specific survival were estimated by adjusted Cox proportional hazards models. Modified landmark approach was applied to avoid immortal time biased results. Among the included CRC patients (n = 3704), 43.6% underwent IRT. Patients who did not live in a relationship with a partner, worked as employee and who reported higher levels of physical activity were more likely to undergo IRT. Patients were less likely to undergo IRT if they had private health insurance, were diagnosed with cancer stage IV, received no or laparoscopic cancer surgery or were treated in a hospital with medium vs. high surgical volume. The median follow-up time was 4.4 years (post-landmark). Utilization of IRT was associated with better overall (HR 0.81, 95% confidence interval 0.72−0.92) and disease-specific survival (HR 0.72, 95% confidence interval 0.61−0.85). Almost every other CRC patient underwent IRT. Next to clinical characteristics, identified social and lifestyle characteristics seemed to play an essential role in the decision-making. Use of IRT was associated with better overall and disease-specific survival. [ABSTRACT FROM AUTHOR]

Summary: Background: The regular use of non‐steroidal anti‐inflammatory drugs (NSAIDs) has been associated with reduced colorectal cancer (CRC) risk. Aim: To explore whether this association varies according to background polygenic risk for CRC. Methods: Data were collected from a large population‐based case‐control study on CRC in Germany. A polygenic risk score (PRS) based on 140 CRC‐related risk loci was used to quantify the genetic risk. The associations of regular use of NSAIDs (≥2times per week for at least 1 year) with CRC risk were estimated in the whole population and in subgroups according to PRS levels using multivariable logistic regression. The impact of NSAIDs on CRC risk was compared to PRS using the 'genetic risk equivalent' (GRE), a recently developed metric for effective risk communication. Results: In total 5129 CRC cases and 4093 controls were included in this analysis. The regular use of NSAIDs (including aspirin) was associated with reduced CRC risk [odds ratio (OR) 0.66, 95% confidence interval (CI) 0.59, 0.74], as was regular use of aspirin only (OR 0.73, 95% CI 0.65, 0.83), without indication of interaction with the PRS (P = 0.10 and 0.22 respectively). The effect of NSAID use was equivalent to the effect of having a 32 percentiles lower PRS (GRE −32, 95% CI −41, −22). Conclusions: The regular use of NSAIDs is associated with greatly reduced CRC risk regardless of individual genetic profile. With an equivalent reduction of relative risk across all polygenic risk groups, absolute risk reduction would be expected to be strongest among those with the highest polygenic risk score. [ABSTRACT FROM AUTHOR]

Screening for lung cancer (LC) by low‐dose computed tomography (LDCT) has been demonstrated to reduce LC mortality in randomized clinical trials (RCTs), and its implementation is in preparation in many countries. However, definition of the target population, which was based on various combinations of age ranges and definitions of heavy smoking in the RCTs, is subject to ongoing debate. Using epidemiological data from Germany, we aimed to estimate prevalence of preclinical LC and positive predictive value (PPV) of LDCT in potential target populations defined by age and smoking history. Populations aged 50 to 69, 55 to 69, 50 to 74 and 55 to 79 years were considered in this analysis. Sex‐specific prevalence of preclinical LC was estimated using LC incidence data within those age ranges and annual transition rates from preclinical to clinical LC obtained by meta‐analysis. Prevalence of preclinical LC among heavy smokers (defined by various pack‐year thresholds) within those age ranges was estimated by combining LC prevalence in the general population with proportions of heavy smokers and relative risks for LC among them derived from epidemiological studies. PPVs were calculated by combining these prevalences with sensitivity and specificity estimates of LDCT. Estimated prevalence of LC was 0.3% to 0.5% (men) and 0.2% to 0.3% (women) in the general population and 0.8% to 1.7% in target populations of heavy smokers. Estimates of PPV of LDCT were <20% for all definitions of target populations of heavy smokers. Refined preselection of target populations would be highly desirable to increase PPV and efficiency of LDCT screening and to reduce numbers of false‐positive LDCT findings. What's new? Lung cancer screening using low‐dose computed tomography (LDCT) is nearing implementation in various countries. However, defining the target population, particularly which individuals will benefit most from LDCT screening, remains a critical issue. Here, using data from Germany, the authors investigated different combinations of age range and smoking history and examined how well these combinations estimated preclinical lung cancer prevalence. Analyses show that expected positive predictive values of lung cancer screening by LDCT were below 20 percent for heavy smokers, within all age ranges investigated. The findings highlight the need for improved target population preselection for lung cancer screening by LDCT. [ABSTRACT FROM AUTHOR]

Background and Aims: Alcohol is a major cancer risk factor and contributes considerably to the cancer burden in Germany. We aimed to provide projections of preventable cancer cases under different price‐based alcohol policy scenarios. Design A macro‐simulation approach was used to estimate numbers and proportions of cancer cases prevented under different price‐based alcohol policy scenarios. Setting and participants: Published price elasticities for main alcoholic beverages were applied to the mean daily intake of pure alcohol in the German population calculated from the German Health Interview and Examination Survey for Adults 2008–11 (DEGS1) to obtain hypothetical exposure distributions of alcohol consumption under different scenarios of changing price for alcoholic beverages. Measurements Age, sex and cancer site‐specific potential impact fractions were calculated for different scenarios of changing the price of alcohol (single price increases, repeated price increases, volumetric price increase) for each year of a 30‐year study period (2020–50). Findings Over a 30‐year horizon, an estimated 4.7% (men = 10.1%, women = 1.4%) of alcohol‐related cancer cases could be prevented in Germany, if alcohol intake above risk thresholds were reduced to levels below risk thresholds. Accordingly, the burden of new cancers would be reduced by approximately 244 000 cases (men = 200 000, women = 44 000). Of all price‐based alcohol policy scenarios, a 100% price increase on alcoholic beverages was estimated to be most effective with approximately 213 000 (4.1%; men = 167 000; women = 47 000) preventable alcohol‐related cancer cases, followed by 5‐yearly 25% price increases (2.8%; men = 115 000, women = 29 000) and a volumetric price increase according to the beverage‐specific alcohol content (1.9%; men = 72 000, women = 24 000). Conclusions: Simulations suggest that a substantial number of alcohol‐related cancer cases could be avoided in Germany by applying price‐based policies to reduce consumption of alcoholic beverages. [ABSTRACT FROM AUTHOR]

Background Vitamin D plays a role in detoxifying free radicals, which might explain the previously reported lower mortality in colorectal cancer (CRC) patients with higher vitamin D concentrations. Objectives We aimed to assess whether the associations of 25-hydroxyvitamin D [25(OH)D] with prognosis in CRC patients differ by total thiol concentration (TTC), a biomarker of antioxidant capacity. Methods CRC patients who were diagnosed from 2003 to 2010 and recruited into a population-based study in southern Germany (n  = 2,592) were followed over a period of 6 y. 25(OH)D and TTC were evaluated from blood samples collected shortly after CRC diagnosis. Associations of 25(OH)D with all-cause and CRC mortality according to TTC were estimated using multivariable Cox proportional hazards regression. Results There was a weak positive correlation between 25(OH)D and TTC (r  = 0.26, P  < 0.001). 25(OH)D was inversely associated with mortality among patients in the lowest and middle TTC tertiles, but no associations were found among patients in the highest TTC tertile (P -interaction = 0.01). Among patients in the lowest/middle TTC tertiles, those in the middle and highest (compared with lowest) 25(OH)D tertiles had 31% and 44% lower all-cause mortality (P  < 0.001) and 25% and 45% lower CRC mortality (P  < 0.001), respectively. However, in the highest TTC tertile, 25(OH)D was not associated with all-cause (P  = 0.638) or CRC mortality (P = 0.395). Conclusions The survival advantages in CRC patients with adequate vitamin D strongly depend on antioxidant capacity and are most pronounced in cases of low antioxidant capacity. These findings suggest that TTC and other biomarkers of antioxidant status may be useful as the basis for enhanced selection criteria of patients for vitamin D supplementation, in addition to the conventional judgment based on blood 25(OH)D concentrations, and also for refining selection of patients for clinical trials aiming to estimate the effect of vitamin D supplementation. [ABSTRACT FROM AUTHOR]

Background: The use of colonoscopy has increased and colorectal cancer (CRC) incidence has decreased after the introduction of screening colonoscopy in Germany. However, it remains unknown to what extent progress has been achieved in the prevention of cancer in the proximal colon, distal colon, and rectum. Methods: We analyzed trends in CRC incidence (2000--2016) and mortality (2000--2018) in Germany by sex, age, and tumor location. Results: The age-standardized incidence of CRC declined by 22.4% (from 65.3 to 50.7 per 100 000) in men and by 25.5% (from 42.7 to 31.8 per 100 000) in women. CRC mortality declined by 35.8% (from 29.6 to 19.0 per 100 000) in men and by 40.5% (19.0 to 11.3 per 100 000) in women. Despite demographic changes, the annual numbers of CRC cases and deaths still decreased from about 60 400 to 58 300 and from around 28 700 to 24 200, respectively. The decline in incidence was greatest in groups aged ≥ 55 years. While the incidence of cancer in the distal colon and rectum decreased by 34.5% and 26.2%, respectively, in men and by 41.0% and 27.9% in women, the incidence of proximal colon cancer remained stable in men and decreased by only 7.0% in women. However, a major shift towards earlier stages was observed for the proximal cancers. Conclusion: The results support the assumption that the increased use of colonoscopy has contributed to substantial reductions in the incidence of distal CRC incidence and the mortality from cancers in the entire colon and rectum. [ABSTRACT FROM AUTHOR]

Simulation models are a powerful tool to overcome gaps of evidence needed to inform medical decision‐making. Here, we present development and application of COSIMO, a Markov‐based Colorectal Cancer (CRC) Multi‐state Simulation Model to simulate effects of CRC screening, along with a thorough assessment of the model's ability to reproduce real‐life outcomes. Firstly, we provide a comprehensive documentation of COSIMO's development, structure and assumptions. Secondly, to assess the model's external validity, we compared model‐derived cumulative incidence and prevalences of colorectal neoplasms to (a) results from KolosSal, a study in German screening colonoscopy participants, (b) registry‐based estimates of CRC incidence in Germany, and (c) outcome patterns of randomized sigmoidoscopy screening studies. We found that (a) more than 90% of observed prevalences in the KolosSal study were within the 95% confidence intervals of the model‐predicted neoplasm prevalences; (b) the 15‐year cumulative CRC incidences estimated by simulations for the German population deviated by 0.0% to 0.2% units in men and 0.0% to 0.3% units in women when compared to corresponding registry‐derived estimates; and (c) the time course of cumulative CRC incidence and mortality in the modeled intervention group and control group closely resembles the time course reported from sigmoidoscopy screening trials. Overall, COSIMO adequately predicted colorectal neoplasm prevalences and incidences in a German population for up to 25 years, with estimated patterns of the effect of screening colonoscopy resembling those seen in registry data and real‐world studies. This suggests that the model may represent a valid tool to assess the comparative effectiveness of CRC screening strategies. What's new? Optimal long‐term strategies for colorectal cancer (CRC) screening, in which health outcomes are balanced with resource use and test burden, remain largely undefined. In this study, to fill‐in evidence gaps and better inform long‐term CRC screening, the authors document the development a model simulating the effects of CRC screening and assessed the model's validity in a large screening colonoscopy study from Germany. The model predicted natural history of CRC for up to 25 years and successfully reproduced screening effects observed in real‐world data. The simulation model is a promising transparent, valid tool, with potential to facilitate medical decision‐making on CRC screening strategies. [ABSTRACT FROM AUTHOR]

Purpose: Chronic pain is common in the older population and a significant public health concern. However, comprehensive studies on analgesics use in this age group from Germany are scarce. This study aims to give a comprehensive overview on the use of the most common therapeutic groups of analgesics in community-dwelling older adults from Germany. Methods: A cross-sectional study was carried out using data from a German cohort of 2038 community-dwelling adults aged 63–89 years. Descriptive statistics and logistic regression models were applied to assess the utilization of analgesics by age, sex, pain severity, pain duration, and locations. Results: One out of four study participants was suffering from high-intensity or disabling pain. Approximately half of those taking analgesics still reported to suffer from high-intensity or disabling pain. Among analgesics users, occasional non-steroidal anti-inflammatory drugs (NSAIDs) use was the most frequent pain therapy (in 43.6% of users), followed by metamizole (dipyrone) use (16.1%), regular NSAIDs use (12.9%), strong opioids use (12.7%), and weak opioids use (12.0%). In multivariate logistic regression models, higher age, higher pain severity, longer pain duration, abdominal pain, and back pain were statistically significantly associated with opioids use. Metamizole use was also statistically significantly associated with higher pain severity but inversely associated with pain duration. Conclusions: A significant number of older German adults are affected by high-intensity and disabling chronic pain despite receiving analgesics. Long-term studies are needed to compare the effectiveness and safety of different treatments for chronic pain in older adults. [ABSTRACT FROM AUTHOR]

Oxidative stress has been implicated in the initiation of several cancers, including colorectal cancer (CRC). Whether it also plays a role in CRC prognosis is unclear. We assessed the associations of two oxidative stress biomarkers (Diacron's reactive oxygen metabolites [d‐ROMs] and total thiol level [TTL]) with CRC prognosis. CRC patients who were diagnosed in 2003 to 2012 and recruited into a population‐based study in Germany (n = 3361) were followed for up to 6 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations of d‐ROMs and TTL (measured from blood samples collected shortly after CRC diagnosis) with overall survival (OS) and disease‐specific survival (DSS) were estimated using multivariable Cox regression. Particularly pronounced associations of higher d‐ROMs with lower survival were observed in stage IV patients, with patients in the highest (vs lowest) tertile having much lower OS (HR = 1.52, 95% CI = 1.14‐2.04) and DSS (HR = 1.61, 95% CI = 1.20‐2.17). For TTL, strong inverse associations of TTL with mortality were observed within all stages. In patients of all stages, those in the highest (vs lowest) quintile had substantially higher OS (HR = 0.48, 95% CI = 0.38‐0.62) and DSS (HR = 0.52, 95% CI = 0.39‐0.69). The addition of these biomarkers to models that included age, sex, tumor stage and subsite significantly improved the prediction of CRC prognosis. The observed strong associations of higher d‐ROMs and lower TTL levels with poorer prognosis even in stage IV patients suggest that oxidative stress contributes significantly to premature mortality in CRC patients and demonstrate a large potential of these biomarkers in enhancing the prediction of CRC prognosis beyond tumor stage. What's new? Oxidative stress has been implicated in the initiation of several cancers, including colorectal cancer (CRC). Whether oxidative stress also plays a role in CRC prognosis remains unclear, however. In this large CRC patient cohort study, higher reactive oxygen metabolites and lower total thiol levels were strongly associated with poorer prognosis. The addition of these biomarkers to models that included age, sex, tumor stage, and sub‐site significantly improved the prediction of CRC prognosis. The findings suggest that oxidative stress contributes significantly to premature mortality in CRC patients and demonstrate the potential of these biomarkers in enhancing the prediction of CRC prognosis. [ABSTRACT FROM AUTHOR]

Evidence on volume outcome associations for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) is limited. We investigated ASCT utilization patterns and volume outcome associations in the German National Registry for Stem Cell Transplants (DRST). MM patients with an upfront ASCT between 1998 and 2014 registered in the DRST were included. ASCT utilization increased strongly from 6% to 17% between 1999 and 2013 with the largest increase for patients aged 60–64 years (8–34%). The mean number of ASCTs conducted in the hospitals per year varied (quintiles, Q1:0.0–8.2 to Q5:31.0–102.7). Center volume was not associated with survival after upfront ASCT (lowest vs. highest center volume, hazard ratios and 95% confidence intervals: 0.95 (0.76–1.18), p = 0.92). Our findings may reflect a high standard of care and degree of specialization of centers performing ASCT for MM in Germany. [ABSTRACT FROM AUTHOR]

Evidence on survival of malignant mesothelioma (MM) and other rare thoracic cancers is limited due to the rarity of these cancer sites. Here, we provide a comprehensive overview of MM incidence and survival after MM and other rare thoracic cancers in Germany and the United States (US). Incidence was estimated from a German National Cancer Database and from the Surveillance, Epidemiology and End Results (SEER) 18 database for 2000–2014. Patients diagnosed in 1997–2013 with malignant epithelial tumors of the trachea (Etra), epithelial tumors of the thymus (Ethy) and MM were extracted from a German cancer survival database and from the SEER 13 database. Period analysis was employed to compute 5‐year relative survival (RS). During 2000–2014, an annual average of 0.9 and 0.6 MM cases per 100,000 person‐years was diagnosed in Germany and the US. Rates decreased in Germany and in the US. Patients with Ethy had highest 5‐year RS with US patients surviving longer (69.1% compared to 63.7%, p = 0.02). Survival after Etra was comparable in both countries (Germany 33.6%, US 34.4%, p = 0.07). Survival in MM patients was poor overall (Germany 11.8%, US 12.1%, p < 0.01). Survival improvements were only observed in MM patients in Germany (10.8% [2002–2007] vs. 13.0% [2008–2013], p < 0.01). The lack of progress in survival for Etra and Ethy patients underlines the need of novel preventive, therapeutic and diagnostic approaches. MM incidence significantly decreased in Germany and in the US. Further monitoring of MM incidence is warranted given that a peak in incidence is expected in 2020–2030 in Western countries. What's new? Certain cancer types that originate from the epithelial or mesothelial tissues of the thoracic cavity are exceedingly rare. As a consequence, little is known about their incidence and survival. Here, utilizing national databases, the authors estimated incidence and survival of malignant mesothelioma (MM) and other rare thoracic cancers in Germany and the United States. Analyses show that between 2000 and 2014, MM incidence declined in both countries, although only MM survival improved in Germany. No improvements were observed in either country for survival of epithelial tumors of the trachea and thymus, highlighting a need for preventive and therapeutic advances. [ABSTRACT FROM AUTHOR]

Postmenopausal hormone replacement therapy (HRT) was found to be associated with lower risk of colorectal cancer (CRC). However, little is known regarding associations with molecular subtypes of CRC. The current study includes female participants of a large German population‐based case–control study (922 CRC cases and 1,183 controls). Tumor tissue samples were analyzed for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), BRAF and KRAS mutation status. Multivariable logistic regression models were used to assess the association of HRT use with molecular subtypes and pathways. Postmenopausal HRT use was overall associated with reduced risk of CRC (adjusted odds ratio (aOR) 0.62, 95% confidence interval (CI) 0.50–0.76) and no major differences were observed for molecular subtypes or for tumor marker combinations representing molecular pathways. When stratified by median age (≤/>71 years) potentially stronger risk reductions were observed in the older group for subtypes showing MSI (OR = 0.36, 95% CI 0.17–0.76), BRAF mutation (OR = 0.40, 95% CI 0.30–0.83) and CIMP‐high (OR = 0.40, 95% CI 0.21–0.73) and for CRC suggestive of the sessile serrated pathway (OR = 0.45, 95% CI 0.20–1.01). In conclusion, postmenopausal use of HRT was similarly associated with risk reduction of major molecular tumor subtypes and pathways of CRC. Potentially stronger risk reductions with CRC subtypes diagnosed at higher ages require confirmation and clarification from other studies. The current study extends the limited understanding of the mechanisms of HRT in CRC prevention. What's new? Evidence suggests that among women, risk of colorectal cancer (CRC) may be reduced by hormone replacement therapy (HRT). Little is known, however, about the impact of HRT on the risk of specific CRC molecular subtypes. In this analysis of female study participants in Germany, postmenopausal use of HRT was associated with a reduction in risk of major molecular subtypes of CRC, namely those characterized by microsatellite instability, CpG island methylator phenotype, or BRAF or KRAS mutations. Risk reductions were strongest for CRC subtypes diagnosed at older ages. The findings expand upon current knowledge of HRT mechanisms in CRC prevention. [ABSTRACT FROM AUTHOR]

Background: Cancer-related fatigue represents one major cause of reduced quality of life in cancer patients and can seriously affect the physical, emotional, and cognitive functioning impeding coping with the disease. Options for effective treatment of cancer-related fatigue are limited, consisting only of non-pharmacologic interventions like physical activity, psychosocial, and mind-body interventions. Recent evidence suggests that vitamin D3 supplementation might alleviate cancer-related fatigue. However, confirmation in a randomized controlled trial is needed.Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 456 colorectal cancer (CRC) patients aged 18 years and older are being recruited in three German rehabilitation clinics. Study inclusion requires hospitalization of at least 3 weeks at such a clinic, a diagnosis of non-metastatic CRC (stage I-III), surgical removal of the tumor within the past 9 months, and season-adapted vitamin D insufficiency or deficiency. Eligible patients are randomly assigned to a personalized regimen of vitamin D3 or placebo for 12 weeks. In the intervention group, a loading dose of 20,000 or 40,000 IU vitamin D3 will be administered daily during the first 11 days, followed by a maintenance dose of 2000 IU daily. Patients will complete questionnaires for secondary outcomes (fatigue subdomains, quality of life and subdomains, depression, functional well-being, and infection frequency). Blood and urine samples will be collected for analyses of safety parameters (hypervitaminosis D, hypercalcemia, hypercalciuria, and renal impairment) and efficacy biomarkers (25-hydroxyvitamin D, HbA1c, white blood cell count, leukocyte subtype counts, serum C-reactive protein, uric acid, creatinine, triglycerides, total, low- and high-density lipoprotein cholesterol).Discussion: This trial tests whether a personalized vitamin D3 dosing regimen reduces or prevents fatigue among non-metastatic CRC patients by treating the underlying vitamin D deficiency/insufficiency. If efficacy can be confirmed, personalized vitamin D3 supplementation could be used as a tertiary prevention measure in addition to non-pharmacological treatments of cancer-related fatigue in CRC patients. We expect to detect an effect of vitamin D3 supplementation on secondary outcomes like quality of life, depression, functional well-being, infections, inflammatory biomarkers, diabetes mellitus, and dyslipidemia.Trial Registration: European Clinical Trials Database: EudraCT-No: 2019-000502-30, January 21, 2019; German Clinical Trials Register (DRKS): DRKS00019907 , April 30, 2019. [ABSTRACT FROM AUTHOR]

Background: The current organized screening program for colorectal cancer in Germany offers both sexes 5 annual fecal immunochemical tests (FITs) between ages 50 and 54 years, followed by a first screening colonoscopy at age 55 years if all of these FITs were negative. We sought to assess the implications of this approach for key parameters of diagnostic performance. Methods and findings: Using a multistate Markov model, we estimated the expected detection rates of advanced neoplasms (advanced adenomas and cancers) and number needed to scope (NNS) to detect 1 advanced neoplasm at a first screening colonoscopy conducted at age 55 after 5 preceding negative FITs and compared them with the corresponding estimates for a first screening colonoscopy at age 55 with no preceding FIT testing. In individuals with 5 consecutive negative FITs undergoing screening colonoscopy at age 55, expected colonoscopy detection rate (NNS) was 3.7% (27) and 0.10% (1,021) for any advanced neoplasm and cancer, respectively, in men, and 2.1% (47) and 0.05% (1,880) for any advanced neoplasm and cancer, respectively, in women. These NNS values for detecting 1 advanced neoplasm are approximately 3-fold higher, and the NNS values for detecting 1 cancer are approximately 8-fold higher, than those for a first screening colonoscopy at age 55 without prior FITs. This study is limited by model simplifying assumptions and uncertainties related to input parameters. Conclusions: Screening colonoscopy at age 55 after 5 consecutive negative FITs at ages 50–54, as currently offered in the German cancer early detection program, is expected to have very low positive predictive value. Our results may inform efforts to enhance the design of screening programs. Thomas Heisser and colleagues model outcomes from colorectal cancer screening in Germany. Author summary: Why was this study done?: The current screening approach for colorectal cancer (CRC) in Germany offers both men and women 5 annual fecal immunochemical tests (FITs, a test for blood in stool) at ages 50–54, followed by a first screening colonoscopy at age 55 in case all of these FITs were negative. The expected result of this sequential screening strategy is unknown. What did the researchers do and find?: In a simulated population of 100,000 men and 100,000 women, colonoscopy detection rates for cancer at age 55 were at or below 0.10% for both sexes after 5 consecutive negative FITs. Looked at another way, 1,000 colonoscopies would be needed in men and 1,900 colonoscopies would be needed in women to detect 1 CRC. These numbers are 8-fold higher than those for a first screening colonoscopy at age 55 without prior FITs. What do these findings mean?: Although annual FITs at ages 50–54 may contribute to earlier diagnosis of CRC, the current sequence of CRC screening, if fully adhered to, may not use screening capacities in the most efficient manner. Our results should inform and encourage efforts to design more rational sequences of screening offers. [ABSTRACT FROM AUTHOR]

Background: Risk stratification for lung cancer (LC) screening is so far mostly based on smoking history. This study aimed to assess if and to what extent such risk stratification could be enhanced by additional consideration of genetic risk scores (GRSs) and epigenetic risk scores defined by DNA methylation. Methods: We conducted a nested case-control study of 143 incident LC cases and 1460 LC-free controls within a prospective cohort of 9949 participants aged 50–75 years with 14-year follow-up. Lifetime smoking history was obtained in detail at recruitment. We built a GRS based on 31 previously identified LC-associated single-nucleotide polymorphisms (SNPs) and a DNA methylation score (MRS) based on methylation of 151 previously identified smoking-associated cytosine-phosphate-guanine (CpG) loci. We evaluated associations of GRS and MRS with LC incidence by logistic regression models, controlling for age, sex, smoking status, and pack-years. We compared the predictive performance of models based on pack-years alone with models additionally including GRS and/or MRS using the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: GRS and MRS showed moderate and strong associations with LC risk even after comprehensive adjustment for smoking history (adjusted odds ratio [95% CI] comparing highest with lowest quartile 1.93 [1.05–3.71] and 5.64 [2.13–17.03], respectively). Similar associations were also observed within the risk groups of ever and heavy smokers. Addition of GRS and MRS furthermore strongly enhanced LC prediction beyond prediction by pack-years (increase of optimism-corrected AUC among heavy smokers from 0.605 to 0.654, NRI 26.7%, p = 0.0106, IDI 3.35%, p = 0.0036), the increase being mostly attributable to the inclusion of MRS. Conclusions: Consideration of MRS, by itself or in combination with GRS, may strongly enhance LC risk stratification. [ABSTRACT FROM AUTHOR]

Background: Participation rates in colorectal cancer screening in Germany are low. We therefore investigated the effectiveness of different invitation models for immunological stool blood tests (fecal immunological tests, FITs). Methods: A randomized controlled trial in 50- to 54-year-old clients of the health insurance provider AOK Baden-Wuerttemberg. A total of 17 532 insured persons were randomized to receive: (A) an invitation letter including a FIT (n = 5850); (B) an invitation letter including an option to request a FIT (n = 5844); or (C) an invitation letter only (n = 5838; control group, routine practice). Reminder letters were sent to half the members of groups A and B, selected at random, after 4 weeks. The primary endpoint was the use of a FIT within 1 year of the date of the invitation letter. IRRID: RR2-10.2196/16413. Registration: DRKS00011858. Results: The invitation letter with a FIT enclosed (A) increased usage from 10% to 29.7% compared with the control group (+19.7% points, p < 0.0001; men: +19.4%, women: +18.8%). The invitation letter with a FIT request option (B) increased usage from 10% to 27.7% (+17.7% points, p < 0.0001; men: +17.7%, women: +17.4%). Reminders increased usage in group A by 7.5% points and in group B by 8.5% points. Participation among women was higher than among men in all groups. The FIT positivity rate was 6.9%. A subsequent colonoscopy was reported for 64.3% of FIT-positive participants, and advanced neoplasia was found in 21.3% of these cases. Conclusion: Letters of invitation that include a FIT and those that offer low-threshold access to a FIT achieve strong, comparable increases in the usage of FIT in the context of colorectal cancer screening. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PC) and its treatment may affect PC survivors differently with respect to age. However, little is known regarding age-specific health-related quality of life (HRQoL) in PC survivors 5 years or even ≥ 10 years post-diagnosis.Methods: The sample included 1975 disease-free PC survivors (5-16 years post-diagnosis) and 661 cancer-free population controls, recruited from two German population-based studies (CAESAR+, LinDe). HRQoL in both populations was assessed using the EORTC QLQ-C30 questionnaire. Additionally, PC survivors completed the PC-specific EORTC QLQ-PR25 questionnaire. Differences in HRQoL between survivors and controls, as well as differences according to age and time since diagnosis were analyzed with multiple regression after adjustment for age, education, stage, and time since diagnosis, where appropriate.Results: In general, PC survivors reported HRQoL and symptom-burden levels comparable to the general population, except for significantly poorer social functioning and higher burden for diarrhea and constipation. In age-specific analyses, PC survivors up to 69 years indicated poorer global health and social functioning than population controls. Stratification by time since diagnosis revealed little difference between the subgroups. On PC-specific symptoms, burden was highest for urinary bother and symptoms, and lowest for bowel symptoms. Younger age was associated with less urinary symptoms but higher urinary bother.Conclusion: Long-term disease-free PC survivors reported overall good HRQoL, but experienced persistent specific detriments. Our data suggest that these detriments do not improve substantially with increasing time since diagnosis. Targeted interventions are recommended to prevent PC-related and treatment-related symptoms becoming chronic and to enhance social functioning. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic inequalities in colorectal cancer survival have been observed in many countries. To overcome these inequalities, the underlying reasons must be disclosed. Methods: Using data from three population-based clinical cancer registries in Germany, we investigated whether associations between area-based socioeconomic deprivation and survival after colorectal cancer depended on patient-, tumor- or treatment-related factors. Patients with a diagnosis of colorectal cancer in 2000–2015 were assigned to one of five deprivation groups according to the municipality of the place of residence using the German Index of Multiple Deprivation. Cox proportional hazards regression models with various levels of adjustment and stratifications were applied. Results: Among 38,130 patients, overall 5-year survival was 4.8% units lower in the most compared to the least deprived areas. Survival disparities were strongest in younger patients, in rectal cancer patients, in stage I cancer, in the latest period, and with longer follow-up. Disparities persisted after adjustment for stage, utilization of surgery and screening colonoscopy uptake rates. They were mostly still present when restricting to patients receiving treatment according to guidelines. Conclusion: We observed socioeconomic inequalities in colorectal cancer survival in Germany. Further studies accounting for potential differences in non-cancer mortality and exploring treatment patterns in detail are needed. [ABSTRACT FROM AUTHOR]

In October 2002, screening colonoscopy was added to the German colorectal cancer (CRC) screening program as an alternative to fecal occult blood test (FOBT). We aimed to evaluate the change in CRC screening use after introduction of the dual screening offer and to assess determinants of screening use. Data were drawn from a population‐based cohort study initiated during 2000–2002 in Germany (n = 5,845, age range at recruitment: 50–75 years). We conducted both cross‐sectional and longitudinal analyses to obtain uptake rates of CRC screening based on four waves of data. Age‐group specific proportions of participants having had FOBT within 2 years remained essentially unchanged at 61–67% between 2000 and 2002 (1st wave) and 2005–2007 (3rd wave). The proportions of participants having undergone screening colonoscopy within 10 years increased from 23–29% to 46–57%, leading to a substantial overall increase in being up‐to‐date with CRC screening from 66–68% to 77–80%. In 2008–2010 (4th wave), FOBT use declined and colonoscopy use continued to increase. Obesity was significantly associated with lower prevalence of being up‐to‐date with FOBT (odds ratio [OR] at 8‐year follow‐up 0.68; 95% confidence interval [CI], 0.58–0.80) and screening colonoscopy (OR, 0.73; 95% CI, 0.62–0.86). Also, smokers were less likely to have ever used FOBT (OR, 0.54; 95% CI, 0.40–0.75) or colonoscopy (OR, 0.75; 95% CI, 0.63–0.90) compared to nonsmokers. After the introduction of dual screening offer, the overall adherence to CRC screening steeply increased, mainly due to an increase in screening colonoscopy uptake. Screening tests kept being underused by obese people and smokers who are at elevated CRC risk. What's new? Colorectal cancer (CRC) screening programs may offer one or more types of screening exam, such as fecal occult blood test (FOBT) or colonoscopy. In this population‐based study in Germany, carried out from 2000‐2010, the addition of colonoscopy as an alternative screening option to FOBT was associated with enhanced overall adherence to CRC screening. Regardless of modality offered, however, CRC screening use remained low among smokers and obese individuals, despite elevated CRC risk in these groups. The results potentially can be used to inform efforts to optimize screening strategies for the best possible reduction in CRC incidence and mortality. [ABSTRACT FROM AUTHOR]

Background Observational studies have consistently shown that a high BMI is associated with increased risk of colorectal cancer (CRC). However, the underlying mechanisms linking obesity to CRC remain unclear. Objectives To investigate the associations of BMI and CRC by major molecular pathological subtypes of CRC. Methods This analysis included 2407 cases and 2454 controls from a large German population–based case–control study. Information on recent weight and height as well as other demographic and lifestyle data were obtained by standardized interviews. Multinomial logistic regression was used to estimate ORs and 95% CIs for the associations between BMI and risk of CRC by major molecular pathological features: microsatellite instability (MSI), CpG island methylator phenotype (CIMP), B- Raf proto-oncogene serine/threonine kinase (BRAF) mutation, and Kirsten rat sarcoma viral oncogene homolog gene (KRAS) mutation. Results Among women, a higher BMI was differentially and more strongly associated with risk of MSI CRC (OR per 5 kg/m2: 1.69; 95% CI: 1.34, 2.12; P heterogeneity ≤ 0.001), CIMP-high CRC (OR per 5 kg/m2: 1.57; 95% CI: 1.30, 1.89; P heterogeneity ≤ 0.001), BRAF -mutated CRC (OR per 5 kg/m2: 1.56; 95% CI: 1.22, 1.99; P heterogeneity = 0.04), and KRAS -wildtype CRC (OR per 5 kg/m2: 1.35; 95% CI: 1.17, 1.54; P heterogeneity = 0.01), compared with the risk of CRC in subjects with the molecular feature counterpart. In men, no meaningful differences in CRC risk were observed for the investigated molecular feature pairs. For the association of BMI with MSI CRC, we observed effect modification by sex (P interaction = 0.04). Also, in women, the risk of CRC with the serrated pathway features was more strongly increased with higher BMI than risk of CRC with the traditional pathway features (OR per 5 kg/m2: 1.73; 95% CI: 1.28, 2.34; P heterogeneity = 0.01). Conclusions In women, the relation between BMI and MSI-high CRC seems to be stronger than that between BMI and microsatellite-stable CRC. However, a validation in an independent cohort is needed. This observational study was registered at the German Clinical Trials Register (http://www.drks.de; study ID: DRKS00011793), an approved primary register in the WHO network. [ABSTRACT FROM AUTHOR]

Early detection of colorectal neoplasms can reduce the disease burden of colorectal cancer by timely intervention of individuals at high risk. Our aim was to evaluate a joint environmental‐genetic risk score as a risk stratification tool for early detection of advanced colorectal neoplasm (ACRN). Known environmental risk factors and high‐risk genetic loci were summarized into risk scores for ACRN in 1014 eligible participants of a screening study. The performances of single and joint environmental‐genetic scores were evaluated with estimates and 95% confidence intervals (CI) of the absolute risk, relative risk and predictive ability using the area under the curve (AUC). Individuals with higher environmental risk scores showed increasing ACRN risk, with 3.1‐fold for intermediate risk and 4.8‐fold for very high risk, compared to the very low environmental risk group. Similarly, individuals with higher genetic risk scores showed increasing ACRN risk, with 2.2‐fold for intermediate risk and 3.5‐fold for very high risk, compared to the lowest genetic risk group. Moreover, the joint environmental–genetic score improved the ACRN risk stratification and showed higher predictive values (AUC = 0.64; 95%CI = 0.60–0.67) with substantial difference (p = 0.0002) compared to the single environmental score (0.58; 0.55–0.62). The integration of environmental and genetic factors looks promising for improving targeting individuals at high‐risk of colorectal neoplasm. Applications in practical screening programs require optimization with additional genetic and other biomarkers involved in colorectal carcinogenesis. What's new? Risk scores based on either environmental (ERS) or genetic (GRS) factors can facilitate efforts to predict colorectal cancer (CRC) risk. Whether these scores combined would prove more effective for CRC risk prediction is unknown. Here, the utility of joint environmental‐genetic risk scores (ERS‐GRS) for risk stratification of advanced colorectal neoplasm (ACRN) was investigated in screening colonoscopy study participants in Germany. Individually, elevated ERS or GRS was associated with increased ACRN risk. Compared to either risk score alone, however, joint ERS‐GRS showed higher prediction performance, suggesting that the integration of these scores can potentially improve CRC risk stratification and prediction. [ABSTRACT FROM AUTHOR]

We critically examined existing approaches for the estimation of the excess familial risk of cancer that can be attributed to identified common genetic risk variants and propose an alternative, more straightforward approach for calculating this proportion using well‐established epidemiological methodology. We applied the underlying equations of the traditional approaches and the new epidemiological approach for colorectal cancer (CRC) in a large population‐based case–control study in Germany with 4,447 cases and 3,480 controls, who were recruited from 2003 to 2016 and for whom interview, medical and genomic data were available. Having a family history of CRC (FH) was associated with a 1.77‐fold risk increase in our study population (95% CI 1.52–2.07). Traditional approaches yielded estimates of the FH‐associated risk explained by 97 common genetics variants from 9.6% to 23.1%, depending on various assumptions. Our alternative approach resulted in smaller and more consistent estimates of this proportion, ranging from 5.4% to 14.3%. Commonly employed methods may lead to strongly divergent and possibly exaggerated estimates of excess familial risk of cancer explained by associated known common genetic variants. Our results suggest that familial risk and risk associated with known common genetic variants might reflect two complementary major sources of risk. What's new? Today's methods to evaluate excess familial risk of cancer explained by associated known common genetic variants may lead to strongly divergent and possibly exaggerated estimates. This paper presents an alternative, more straightforward approach using well‐established epidemiological methodology. Application in a large population‐based case–control study in colorectal cancer supports suggestions that this proportion may be substantially smaller than previously assumed and highly dependent on SNP pruning methods, the assumed risk for having a family history of CRC, and the number of identified SNPs. Rather than reflecting a major subcomponent of familial risk, common genetic variants appear to reflect substantial complementary risk. [ABSTRACT FROM AUTHOR]

Objective potentially inappropriate medications (PIMs) are commonly defined as drugs that should be avoided in older adults because they are considered to have a negative risk-benefit ratio. PIMs are suspected to increase the risk for frailty, but this has yet to be examined. Design prospective population-based cohort study. Setting and participants a German cohort of community-dwelling older adults (≥60 years) was followed from October 2008 to September 2016. Methods in propensity score-adjusted logistic and Cox regression models, associations between baseline PIM use and prevalent/incident frailty were investigated. Frailty was assessed using the definition by Fried and co-workers, PIM were defined with the 2015 BEERS criteria , the BEERS criteria to avoid in cognitively impaired patients (BEERS dementia PIM), the EU(7)-PIM and the PRISCUS list. Results of 2,865 participants, 261 were frail at baseline and 423 became frail during follow-up. Only BEERS dementia PIM use was statistically significantly associated with prevalent frailty (odds ratio (95% confidence interval), 1.51 (1.04–2.17)). The strength of the association was comparable for all frailty components. Similarly, in longitudinal analyses, only BEERS dementia PIM use was associated with incident frailty albeit not statistically significant (hazard ratio, 1.19 (0.84–1.68)). Conclusions the association of PIM use and frailty seems to be restricted to drug classes, which can induce frailty symptoms (anticholinergics, benzodiazepines, z-substances and antipsychotics). Physicians are advised to perform frailty assessments before and after prescribing these drug classes to older patients and to reconsider treatment decisions in case of negative performance changes. [ABSTRACT FROM AUTHOR]

Objective: Oxidative stress is believed to play an important role in the pathophysiology of type 2 diabetes, but the few cohort studies that have assessed the association of oxidative stress biomarkers with type 2 diabetes incidence were small and reported inconclusive results.Research Design and Methods: We examined the associations of urinary oxidized guanine/guanosine (OxGua) levels (a biomarker of DNA/RNA oxidation) and urinary 8-isoprostane levels (a biomarker of lipid peroxidation) with type 2 diabetes incidence in 7,828 individuals initially without diabetes from a population-based German cohort study with 14 years of follow-up. Hazard ratios (HRs) (95% CIs) per 1 SD were obtained using multivariable-adjusted Cox proportional hazards regression models.Results: In the total population, weak but statistically significant associations with type 2 diabetes incidence were observed for OxGua levels (HR [95% CI] per 1 SD 1.05 [1.01; 1.09]) and 8-isoprostane levels (1.04 [1.00; 1.09]). Stratified analyses showed that associations of both biomarkers with type 2 diabetes incidence were absent in the youngest age-group (50-59 years) and strongest in the oldest age-group (65-75 years) of the cohort, with HR of OxGua levels 1.14 (1.05; 1.23) per 1 SD and of 8-isoprostane levels 1.22 (1.02; 1.45) per 1 SD.Conclusions: These results from a large cohort study support suggestions that an imbalanced redox system contributes to the development of type 2 diabetes but suggest that this association becomes clinically apparent at older ages only, possibly as a result of reduced cellular repair capacity. [ABSTRACT FROM AUTHOR]

Background/objectives: The aim of the study was to describe a novel dietary assessment strategy based on two instruments complemented by information from an external population applied to estimate usual food intake in the large-scale multicenter German National Cohort (GNC). As proof of concept, we applied the assessment strategy to data from a pretest study (2012-2013) to assess the feasibility of the novel assessment strategy.Subjects/methods: First, the consumption probability for each individual was modeled using three 24 h food lists (24h-FLs) and frequencies from one food frequency questionnaire (FFQ). Second, daily consumed food amounts were estimated from the representative German National Nutrition Survey II (NVS II) taking the characteristics of the participants into account. Usual food intake was estimated using the product of consumption probability and amounts.Results: We estimated usual intake of 41 food groups in 318 men and 377 women. The participation proportion was 100, 84.4, and 68.5% for the first, second, and third 24h-FL, respectively. We observed no associations between the probability of participating and lifestyle factors. The estimated distributions of usual food intakes were plausible and total energy was estimated to be 2707 kcal/day for men and 2103 kcal/day for women. The estimated consumption frequencies did not differ substantially between men and women with only few exceptions. The differences in energy intake between men and women were mostly due to differences in estimated daily amounts.Conclusions: The combination of repeated 24h-FLs, a FFQ, and consumption-day amounts from a reference population represents a user-friendly dietary assessment approach having generated plausible, but not yet validated, food intake values in the pretest study. [ABSTRACT FROM AUTHOR]

Colorectal cancer is known to arise from multiple tumorigenic pathways; however, the underlying mechanisms remain not completely understood. Metabolomics is becoming an increasingly popular tool in assessing biological processes. Previous metabolomics research focusing on colorectal cancer is limited by sample size and did not replicate findings in independent study populations to verify robustness of reported findings. Here, we performed a ultrahigh performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UHPLC‐QTOF‐MS) screening on EDTA plasma from 268 colorectal cancer patients and 353 controls using independent discovery and replication sets from two European cohorts (ColoCare Study: n = 180 patients/n = 153 controls; the Colorectal Cancer Study of Austria (CORSA) n = 88 patients/n = 200 controls), aiming to identify circulating plasma metabolites associated with colorectal cancer and to improve knowledge regarding colorectal cancer etiology. Multiple logistic regression models were used to test the association between disease state and metabolic features. Statistically significant associated features in the discovery set were taken forward and tested in the replication set to assure robustness of our findings. All models were adjusted for sex, age, BMI and smoking status and corrected for multiple testing using False Discovery Rate. Demographic and clinical data were abstracted from questionnaires and medical records. What's new? Colorectal cancer exhibits certain characteristic changes in metabolic pathways. To expand upon previous findings, these authors performed a discovery‐replication study using two large independent study populations from different countries, Germany and Austria. They tested metabolic profiles of cancer patients and controls, identifying 691 statistically significant features in the discovery cohort. Testing the second cohort narrowed it to 97. These corresponded to 28 metabolites, of which 15 could be identified. It will be useful to go forward with prospective analysis on these 15 metabolites, to determine whether they have predictive or prognostic value. [ABSTRACT FROM AUTHOR]

Background: Population-based estimates of the long-term risk of loco-regional recurrence and distant metastases of breast cancer (BRC) patients are scant, as most published studies used hospital-based cohorts or participants of clinical trials. This work aims to extend available knowledge by providing population-based long-term estimates of the cumulative risk of BRC recurrence up to 10 years after diagnosis.Methods: Data from the population-based Saarland Cancer Registry were used and included 9359 female patients with primary invasive BRC diagnosed between 1999 and 2009. Estimates of the cumulative incidence (CI) of BRC recurrence were derived for patients who had received local surgery with free resection margins by type of recurrence and stratified by age, tumor characteristics and major treatment options, taking into account mortality from any cause as a competing risk.Results: The 10-year CI of BRC recurrence was 16%. For loco-regional recurrence and distant metastases alone it was 8 and 11%, respectively. The estimates showed substantial variation and were particularly increased if tumors were advanced (T1/2N+ 23%, T3/4N0 24%, T3/4N+ 34%), of high grade (23%), or of 'HER2/neu positive' (28%) or 'triple negative' subtype (23%), respectively.Conclusions: The derived estimates reflect the risk of 'real world' patients and may therefore extend available knowledge. These data are thus of great relevance for clinicians, their patients and researchers. The study likewise demonstrated the usefulness of cancer registries for a population-based monitoring of the effectiveness of cancer care in terms of disease recurrence as a major treatment related outcome measure. [ABSTRACT FROM AUTHOR]

Importance: Fecal immunochemical tests for hemoglobin are widely used for colorectal cancer (CRC) screening. Observational studies suggested that sensitivity of fecal immunochemical tests for detecting advanced neoplasms could be increased by acetylsalicylic acid (aspirin), especially among men.Objective: To evaluate the potential to increase sensitivity of fecal immunochemical tests by administering a single 300-mg oral aspirin dose 2 days before stool sampling.Design, Setting, and Participants: A randomized, placebo-controlled, double-blind trial was conducted in 14 gastroenterology practices and 4 hospitals in Germany, and included 2422 men and women aged 40 to 80 years scheduled for colonoscopy, with no recent use of aspirin or other drugs with antithrombotic effects (enrollment from June 2013 to November 2016, and final follow-up January 27, 2017).Interventions: Administration of a single tablet containing 300 mg of aspirin (n = 1208) or placebo (n = 1214) 2 days before fecal sampling for fecal immunochemical test.Main Outcome and Measures: The primary outcome was sensitivity of a quantitative fecal immunochemical test at 2 predefined cutoffs (10.2 and 17-μg Hb/g stool) for detecting advanced neoplasms (colorectal cancer or advanced adenoma).Results: Among 2422 randomized patients (mean [SD] age, 59.6 [7.9] years; 1219, 50%, men), 2134 were included in the analysis (78% for primary screening colonoscopy, 22% for diagnostic colonoscopy). Advanced neoplasms were identified in 224 participants (10.5%), including 8 participants (0.4%) with CRC and 216 participants (10.1%) with advanced adenoma. Sensitivity was 40.2% in the aspirin group and 30.4% in the placebo group (difference 9.8%, 95% CI, -3.1% to 22.2%, P = .14) at cutoff 10.2-μg Hb/g stool and 28.6% in the aspirin and 22.5% in the placebo group (difference 6.0%, 95% CI, -5.7% to 17.5%, P = .32) at cutoff 17-μg Hb/g stool.Conclusions and Relevance: Among adults aged 40 to 80 years not using aspirin or other antithrombotic medications, administration of a single dose of oral aspirin prior to fecal immunochemical testing, compared with placebo, did not significantly increase test sensitivity for detecting advanced colorectal neoplasms at 2 predefined cutoffs of a quantitative fecal immunochemical test.Trial registration: Deutsches Register Klinischer Studien Identifier: DRKS00003252; EudraCT Identifier: 2011-005603-32/DE. [ABSTRACT FROM AUTHOR]

Background: With improving prognosis, the ability to return to work after cancer has become a realistic goal but only little is known regarding details such as sustainability, financial consequences, and potential determinants of return to work in long-term survivors in Germany. Methods: We studied return to work in a population-based sample of 1558 long-term cancer survivors, diagnosed in 1994–2004 with breast, colorectal or prostate cancer before age 60 (mean 50.1). Information regarding employment status and financial difficulties was obtained via mailed questionnaires from patients who were identified by six population-based cancer registries in Germany. Cumulative incidence of return to work was determined by time-to-event analysis with consideration of competing events. Chi2 tests and multiple logistic regression modeling were employed to identify potential sociodemographic and clinical determinants of return to work. Results: Within a mean period since diagnosis of 8.3 years, 63% of all working-age cancer survivors initially returned to their old job and another 7% took up a new job. Seventeen percent were granted a disability pension, 6% were early retired (not cancer-related), 4% became unemployed, and 1% left the job market for other reasons. Resumption of work occurred within the first 2 years after diagnosis in 90% of all returnees. Cancer-related reduction of working hours was reported by 17% among all returnees and 6% quit their job due to cancer within 5 years past return to work. The probability of return to work was strongly related with age at diagnosis, tumor stage, education, and occupational class but did not differ with respect to the tumor site, gender nor marital status. Conclusions: Most long-term survivors after breast, colorectal, or prostate cancer of working-age are able to return to work. However, financial problems might arise due to a reduction in working hours. An additional provision of targeted interventions for high-risk groups should be discussed. [ABSTRACT FROM AUTHOR]

Purpose: To assess the changes in use of potentially inappropriate medication (PIM) as defined by the 2015 Beers criteria, the EU(7)-PIM, and the PRISCUS list over a 6-year period and to identify determinants for current and future PIM use with a particular focus on geriatric syndromes.Methods: In a German cohort of 2878 community-dwelling adults aged ≥ 60 years, determinants of the use of ≥ 1 PIM were identified in multivariable logistic regression (cross-sectional analysis) and weighted generalized estimating equation models (longitudinal analysis).Results: Prevalences for Beers, EU(7), and PRISCUS PIM were 26.4, 37.4, and 13.7% at baseline and decreased to 23.1, 36.5, and 12.3%, respectively, 6 years later. Unadjusted prevalences in participants with any geriatric syndrome (frailty, co-morbidity, functional, or cognitive impairment) were approximately twice as high as in robust older adults. In multivariable analyses, cognitive impairment was statistically significantly associated with the use of PIM of all three criteria in the cross-sectional (odds ratio (OR) point estimates 1.90-2.21) but not in the longitudinal models. In contrast, frailty, co-morbidity, and functional impairment were statistically significantly associated with the use of PIM of at least one of the three criteria in both models. However, the associations varied for the PIM criteria, and in the longitudinal analysis, associations were only statistically significant for Beers PIM (ORs [95% confidence intervals]: frailty (2.23 [1.15, 4.31]), co-morbidity by five total co-morbidity score points (1.21 [1.05, 1.38]), and functional impairment (1.51 [1.00, 2.27]). Other statistically significant determinants of the incidence of PIM (any definition) were female sex, age, coronary heart disease, heart failure, biomarkers of the metabolic syndrome, and history of ulcer, depressive episodes, hip fracture, or any cancer.Conclusions: Older adults with frailty, co-morbidity, cognitive, and functional impairment had higher odds of taking PIM or getting a PIM prescription in the future (exception: cognitive impairment). Physicians should be especially cautious when prescribing drugs for these patients who are particularly susceptible to adverse reactions. [ABSTRACT FROM AUTHOR]