A claimed advantage of colonoscopy over sigmoidoscopy in colorectal cancer (CRC) screening is prevention of CRC not only in the distal colon and rectum but also in the proximal colon. We aimed to ...assess the association of screening colonoscopy use with overall and site-specific CRC incidence and associated mortality.
Information on use of screening colonoscopy as well as potential confounding factors was obtained at baseline in 2000-2002, updated at 2-, 5-, 8-, and 17-year follow-up from 9,207 participants aged 50-75 years without history of CRC in a statewide cohort study in Saarland, Germany. Covariate-adjusted associations of screening colonoscopy with CRC incidence and mortality, which were obtained through record linkage with the Saarland Cancer Registry and mortality statistics up to 2018, were assessed by Cox proportional hazards models with time-varying exposure information.
During a median follow-up of 17.2 years, 268 participants were diagnosed with CRC and 98 died from CRC. Screening colonoscopy was associated with strongly reduced CRC incidence (adjusted hazard ratio aHR 0.44, 95% confidence interval CI 0.33-0.57) and mortality (aHR 0.34, 95% CI 0.21-0.53), with stronger reduction for distal (aHRs 0.36, 95% CI 0.25-0.51, and 0.33, 95% CI 0.19-0.59, respectively) than for proximal cancer (aHRs 0.69, 95% CI 0.42-1.13, and 0.62, 95% CI 0.26-1.45, respectively). Nevertheless, strong reduction of mortality from proximal cancer was also observed within 10 years after screening colonoscopy (aHR 0.31, 95% CI 0.10-0.96).
In this large prospective cohort study from Germany, screening colonoscopy was associated with strong reduction in CRC incidence and mortality.
The COVID-19 pandemic goes along with increased mortality from acute respiratory disease. It has been suggested that vitamin D
supplementation might help to reduce respiratory disease mortality. We ...assessed the prevalence of vitamin D insufficiency and deficiency, defined by 25-hydroxyvitamin D (25(OH)D) blood levels of 30-50 and <30 nmol/L, respectively, and their association with mortality from respiratory diseases during 15 years of follow-up in a cohort of 9548 adults aged 50-75 years from Saarland, Germany. Vitamin D insufficiency and deficiency were common (44% and 15%, respectively). Compared to those with sufficient vitamin D status, participants with vitamin D insufficiency and deficiency had strongly increased respiratory mortality, with adjusted hazard ratios (95% confidence intervals) of 2.1 (1.3-3.2) and 3.0 (1.8-5.2) overall, 4.3 (1.3-14.4) and 8.5 (2.4-30.1) among women, and 1.9 (1.1-3.2) and 2.3 (1.1-4.4) among men. Overall, 41% (95% confidence interval: 20-58%) of respiratory disease mortality was statistically attributable to vitamin D insufficiency or deficiency. Vitamin D insufficiency and deficiency are common and account for a large proportion of respiratory disease mortality in older adults, supporting the hypothesis that vitamin D
supplementation could be helpful to limit the burden of the COVID-19 pandemic, particularly among women.
Abstract
Circulating microRNAs (miRNAs) could improve colorectal cancer (CRC) risk prediction. Here, we derive a blood-based miRNA panel and evaluate its ability to predict CRC occurrence in a ...population-based cohort of adults aged 50–75 years. Forty-one miRNAs are preselected from independent studies and measured by quantitative-real-time-polymerase-chain-reaction in serum collected at baseline of 198 participants who develop CRC during 14 years of follow-up and 178 randomly selected controls. A 7-miRNA score is derived by logistic regression. Its predictive ability, quantified by the optimism-corrected area-under-the-receiver-operating-characteristic-curve (AUC) using .632+ bootstrap is 0.794. Predictive ability is compared to that of an environmental risk score (ERS) based on known risk factors and a polygenic risk score (PRS) based on 140 previously identified single-nucleotide-polymorphisms. In participants with all scores available, optimism-corrected-AUC is 0.802 for the 7-miRNA score, while AUC (95% CI) is 0.557 (0.498–0.616) for the ERS and 0.622 (0.564–0.681) for the PRS.
DNA methylation (DNAm) has been revealed to play a role in various diseases. Here we performed epigenome-wide screening and validation to identify mortality-related DNAm signatures in a general ...population-based cohort with up to 14 years follow-up. In the discovery panel in a case-cohort approach, 11,063 CpGs reach genome-wide significance (FDR<0.05). 58 CpGs, mapping to 38 well-known disease-related genes and 14 intergenic regions, are confirmed in a validation panel. A mortality risk score based on ten selected CpGs exhibits strong association with all-cause mortality, showing hazard ratios (95% CI) of 2.16 (1.10-4.24), 3.42 (1.81-6.46) and 7.36 (3.69-14.68), respectively, for participants with scores of 1, 2-5 and 5+ compared with a score of 0. These associations are confirmed in an independent cohort and are independent from the 'epigenetic clock'. In conclusion, DNAm of multiple disease-related genes are strongly linked to mortality outcomes. The DNAm-based risk score might be informative for risk assessment and stratification.
Previous studies have developed models predicting methylation age from DNA methylation in blood and other tissues (epigenetic clock) and suggested the difference between DNA methylation and ...chronological ages as a marker of healthy aging. The goal of this study was to confirm and expand such observations by investigating whether different concepts of the epigenetic clocks in a population-based cohort are associated with cancer, cardiovascular, and all-cause mortality.
DNA methylation age was estimated in a cohort of 1863 older people, and the difference between age predicted by DNA methylation and chronological age (Δage) was calculated. A case-cohort design and weighted proportional Cox hazard models were used to estimate associations of Δage with cancer, cardiovascular, and all-cause mortality. Hazard ratios for Δage (per 5 years) calculated using the epigenetic clock developed by Horvath were 1.23 (95 % CI 1.10-1.38) for all-cause mortality, 1.22 (95 % CI 1.03-1.45) for cancer mortality, and 1.19 (95 % CI 0.98-1.43) for cardiovascular mortality after adjustment for batch effects, age, sex, educational level, history of chronic diseases, hypertension, smoking status, body mass index, and leucocyte distribution. Associations were similar but weaker for Δage calculated using the epigenetic clock developed by Hannum.
These results show that age acceleration in terms of the difference between age predicted by DNA methylation and chronological age is an independent predictor of all-cause and cause-specific mortality and may be useful as a general marker of healthy aging.
Abstract
Objective
to investigate how frailty and frailty symptoms affect healthcare costs in older age longitudinally.
Methods
data were gathered from a prospective cohort study in Saarland, Germany ...(two waves with 3-year interval, n = 1,636 aged 57–84 years at baseline). Frailty was assessed by the five Fried frailty criteria. Frailty was defined as having at least three criteria, the presence of 1–2 criteria as ‘pre-frail’. Healthcare costs were quantified based on self-reported healthcare use in the sectors of inpatient treatment, outpatient treatment, professional nursing care and informal care as well as the provision of pharmaceuticals, medical supplies and dental prostheses.
Results
while the onset of pre-frailty did not increase (log) total healthcare costs after adjusting for potential confounders including comorbidity, progression from non-frailty to frailty was associated with an increase in total healthcare costs (for example, costs increased by ~54 and 101% if 3 and 4 or 5 symptoms were present, respectively). This association of frailty onset with increased healthcare costs was in particular observed in the inpatient sector and for informal nursing care. Among the frailty symptoms, the onset of exhaustion was associated with an increase in total healthcare costs, whereas changes in slowness, weakness, weight loss and low-physical activity were not significantly associated with an increase in total healthcare costs.
Conclusions
our data stress the economic relevance of frailty in late life. Postponing or reducing frailty might be fruitful in order to reduce healthcare costs.
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.
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.
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.
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.
Alzheimer's disease (AD) is currently incurable, but there is general agreement that a minimally invasive blood biomarker for screening in preclinical stages would be crucial for future therapy. ...Diagnostic tools for detection of AD are either invasive like cerebrospinal fluid (CSF) biomarkers or expensive such as positron emission tomography (PET) scanning. Here, we determine the secondary structure change of amyloid‐β (Aβ) in human blood. This change used as blood amyloid biomarker indicates prodromal AD and correlates with CSF AD biomarkers and amyloid PET imaging in the cross‐sectional BioFINDER cohort. In a further population‐based longitudinal cohort (ESTHER), the blood biomarker detected AD several years before clinical diagnosis in baseline samples with a positive likelihood ratio of 7.9; that is, those who were diagnosed with AD over the years were 7.9 times more likely to test positive. This assay may open avenues for blood screening of early AD stages as a funnel for further more invasive and expensive tests.
Synopsis
Determination of the amyloid‐β secondary structure distribution in blood plasma by an immuno‐IR‐sensor correlates with PET scanning and CSF markers in Alzheimer's disease (AD) patients, with potentials to be an accurate, simple, and minimally invasive biomarker for early AD detection.
The amyloid‐β (Aβ) secondary structure distribution in blood plasma can be directly determined by the secondary structure sensitive amide I band.
Prodromal AD cases (BioFINDER study) showed significant correlations between the amide I frequency shift and PET scanning results or CSF biomarker values.
Early AD identification (Esther) yielded in 71% sensitivity, 91% specificity, and a LR+ of 7.9–8 years before clinical symptoms appeared, in agreement with the BioFINDER study.
The plasma biomarker may be used as a routine minimal‐invasive, low‐cost funnel to pre‐select individuals which should undergo lumbar puncture or PET scanning.
Determination of the amyloid‐β secondary structure distribution in blood plasma by an immuno‐IR‐sensor correlates with PET scanning and CSF markers in Alzheimer's disease (AD) patients, with potentials to be an accurate, simple, and minimally invasive biomarker for early AD detection.
Summary Background More effective treatments have become available for haematological malignancies from the early 2000s, but few large-scale population-based studies have investigated their effect on ...survival. Using EUROCARE data, and HAEMACARE morphological groupings, we aimed to estimate time trends in population-based survival for 11 lymphoid and myeloid malignancies in 20 European countries, by region and age. Methods In this retrospective observational study, we included patients (aged 15 years and older) diagnosed with haematological malignancies, diagnosed up to Dec 31, 2007, and followed up to Dec 31, 2008. We used data from the 30 cancer registries (across 20 countries) that provided continuous incidence and good quality data from 1992 to 2007. We used a hybrid approach to estimate age-standardised and age-specific 5-year relative survival, for each malignancy, overall and for five regions (UK, and northern, central, southern, and eastern Europe), and four 3-year periods (1997–99, 2000–02, 2003–05, 2006–08). For each malignancy, we also estimated the relative excess risk of death during the 5 years after diagnosis, by period, age, and region. Findings We analysed 560 444 cases. From 1997–99 to 2006–08 survival increased for most malignancies: the largest increases were for diffuse large B-cell lymphoma (42·0% 95% CI 40·7–43·4 to 55·4% 54·6–56·2, p<0·0001), follicular lymphoma (58·9% 57·3–60·6 to 74·3% 72·9–75·5, p<0·0001), chronic myeloid leukaemia (32·3% 30·6–33·9 to 54·4% 52·5–56·2, p<0·0001), and acute promyelocytic leukaemia (50·1% 43·7–56·2 to 61·9% 57·0–66·4, p=0·0038, estimate not age-standardised). Other survival increases were seen for Hodgkin's lymphoma (75·1% 74·1–76·0 to 79·3% 78·4–80·1, p<0·0001), chronic lymphocytic leukaemia/small lymphocytic lymphoma (66·1% 65·1–67·1 to 69·0% 68·1–69·8, p<0·0001), multiple myeloma/plasmacytoma (29·8% 29·0–30·6 to 39·6% 38·8–40·3, p<0·0001), precursor lymphoblastic leukaemia/lymphoma (29·8% 27·7–32·0 to 41·1% 39·0–43·1, p<0·0001), acute myeloid leukaemia (excluding acute promyelocytic leukaemia, 12·6% 11·9–13·3 to 14·8% 14·2–15·4, p<0·0001), and other myeloproliferative neoplasms (excluding chronic myeloid leukaemia, 70·3% 68·7–71·8 to 74·9% 73·8–75·9, p<0·0001). Survival increased slightly in southern Europe, more in the UK, and conspicuously in northern, central, and eastern Europe. However, eastern European survival was lower than that for other regions. Survival decreased with advancing age, and increased with time only slightly in patients aged 75 years or older, although a 10% increase in survival occurred in elderly patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic myeloid leukaemia. Interpretation These trends are encouraging. Widespread use of new and more effective treatment probably explains much of the increased survival. However, the persistent differences in survival across Europe suggest variations in the quality of care and availability of the new treatments. High-resolution studies that collect data about stage at diagnosis and treatments for representative samples of cases could provide further evidence of treatment effectiveness and explain geographic variations in survival. Funding Compagnia di San Paolo, Fondazione Cariplo, European Commission, and Italian Ministry of Health.
Newly established blood DNA methylation markers that are strongly associated with smoking might open new avenues for lung cancer (LC) screening. We aimed to assess the performance of the top hits ...from previous epigenome-wide association studies in prediction of LC incidence. In a prospective nested case-control study, DNA methylation at
(cg05575921),
(cg06126421), and
(cg03636183) were measured by pyrosequencing in baseline whole blood samples of 143 incident LC cases identified during 11 years of follow-up and 457 age- and sex-matched controls without diagnosis of LC until the end of follow-up. The individual and joint associations of the 3 markers with LC risk were estimated by logistic regression, adjusted for potential confounders including smoking status and cigarette pack-years. The predictive performance was evaluated for both the individual markers and their combinations derived from multiple algorithms.
Pronounced demethylation of all 3 markers was observed at baseline among cases compared to controls. Risk of developing LC increased with decreasing DNA methylation levels, with adjusted ORs (95% CI) of 15.86 (4.18-60.17), 8.12 (2.69-4.48), and 10.55 (3.44-32.31), respectively, for participants in the lowest quartile of
,
, and
compared to participants in the highest 2 quartiles of each site among controls. The individual 3 markers exhibited similar accuracy in predicting LC incidence, with AUCs ranging from 0.79 to 0.81. Combination of the 3 markers did not improve the predictive performance (AUC = 0.80). The individual markers or their combination outperformed self-reported smoking exposure particularly in light smokers. No variation in risk prediction was identified with respect to age, follow-up time, and histological subtypes.
,
, and
methylation in blood DNA are predictive for LC development, which might be useful for identification of risk groups for further specific screening, such as CT examination.
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