Search

The European Policy Evaluation Network (PEN), initiated in autumn 2018, aimed at advancing the evidence base for public policies impacting dietary behaviour, physical activity and sedentary behaviours in Europe. This is needed because non-communicable diseases—the leading cause of global mortality—are substantially caused by physical inactivity and unhealthy dietary behaviours, which in turn are driven by upstream factors that have not yet been addressed effectively by prevention approaches. Thus, successful policy interventions are required that target entire populations and tackle the 'causes of the causes'. To advance our knowledge on the effective implementation of policies and their impact in terms of improving health behaviours, PEN focused on five research tasks: (i) Adaptation and implementation of a Food Environment Policy Index (Food-EPI) and development of a Physical Activity Environment Policy Index (PA-EPI); (ii) Mapping of health-related indicators needed for policy evaluation and facilitating a harmonized pan-European approach for surveillance to assess the impact of policy interventions; (iii) Refining quantitative methods to evaluate the impact of public policies; (iv) Identifying key barriers and facilitators of implementation of policies; and (v) Advance understanding the equity impact of the development, implementation and evaluation of policies aimed at promoting physical activity and a healthy diet. Finally, and in order to provide concrete evidence for policymaking, existing exemplary policies, namely sugar-sweetened beverages taxation, active transport policies and school policies on nutrition and physical activity were assessed in consideration of these five tasks. At the end of the PEN project's formal runtime, considerable advancements have been made. Here, we present an overview of the most important learnings and outputs. [ABSTRACT FROM AUTHOR]

Background: The hormone leptin has been suggested to play a role in the respiratory and immune systems. Evidence on sex‐specific concentrations of leptin in human milk and sex‐specific associations with the development of asthma and wheeze has been put forward but is still scarce. Objective: To investigate whether male and female infants receive different levels of leptin through human milk and whether leptin is implicated in the development of asthma and wheeze in a sex‐dependent manner using data from the two Ulm Birth Cohort studies. Methods: Leptin data were available from human milk samples collected at 6 weeks (Ulm Birth Cohort Study [UBCS, n = 678; Ulm SPATZ Health Study, n = 587]), and, in SPATZ only, at 6 months (n = 377) and 12 months (n = 66) of lactation. Sex‐specific associations with doctor‐diagnosed asthma and wheeze phenotypes were assessed in crude and adjusted models using logistic regression. Adjustments were made for maternal allergy, exclusive breastfeeding, infant age at the time of milk sampling, and child BMI z‐score. Results: At 6 weeks, leptin levels (median [min, max], in ng/L) were higher in the milk for girls (197 [0.100, 4120]) than in milk for boys (159 [1.02, 3280], p =.045) in UBCS. No significant sex differences were observed in SPATZ (p =.152). There were no significant associations of leptin with asthma or wheeze in both studies, even in a sex‐dependent manner (p >.05). Conclusion: It remains unclear whether male and female infants receive different levels of leptin through human milk. However, leptin in human milk may not be associated with history and development of asthma and wheeze in a sex‐specific manner. [ABSTRACT FROM AUTHOR]

Because screening was used by only 58% to 84% of participants in the 4 trials, even substantially higher reduction of incidence would be expected for those participants who actually accepted the screening offer, in line with results from observational studies ([5]). [PMID: 30261804] doi:10.1177/0969141318790775 5 Brenner H, Stock C, Hoffmeister M. Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of randomised controlled trials and observational studies. Focusing on these cases - most of which are likely truly incident cases - would yield an estimated incidence reduction of approximately 30% for any CRC and 50% for distal CRC, which is much higher than the reported 21% and 32% reduction of CRC detection from the time of recruitment. [Extracted from the article]

Background People with cancer experience high rates of venous thromboembolism (VTE). Risk of subsequent cancer is also increased in people experiencing their first VTE. The causal mechanisms underlying this association are not completely understood, and it is unknown whether VTE is itself a risk factor for cancer. Methods We used data from large genome-wide association study meta-analyses to perform bidirectional Mendelian randomization analyses to estimate causal associations between genetic liability to VTE and risk of 18 different cancers. Results We found no conclusive evidence that genetic liability to VTE was causally associated with an increased incidence of cancer, or vice versa. We observed an association between liability to VTE and pancreatic cancer risk [odds ratio for pancreatic cancer: 1.23 (95% confidence interval: 1.08–1.40) per log-odds increase in VTE risk, P =  0.002]. However, sensitivity analyses revealed this association was predominantly driven by a variant proxying non-O blood group, with inadequate evidence to suggest a causal relationship. Conclusions These findings do not support the hypothesis that genetic liability to VTE is a cause of cancer. Existing observational epidemiological associations between VTE and cancer are therefore more likely to be driven by pathophysiological changes which occur in the setting of active cancer and anti-cancer treatments. Further work is required to explore and synthesize evidence for these mechanisms. [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]

Colorectal cancer (CRC) is both one of the most common and one of the most preventable cancers globally, with powerful but strongly missed potential for primary, secondary and tertiary prevention. CRC incidence has traditionally been the highest in affluent Western countries, but it is now increasing rapidly with economic development in many other parts of the world. CRC shares several main risk factors, such as smoking, excessive alcohol consumption, physical inactivity and being overweight, with other common diseases; therefore, primary prevention efforts to reduce these risk factors are expected to have multiple beneficial effects that extend beyond CRC prevention, and should have high public health impact. A sizeable reduction in the incidence and mortality of CRC can also be achieved by offering effective screening tests, such as faecal immunochemical tests, flexible sigmoidoscopy and colonoscopy, in organised screening programmes which have been implemented in an increasing number of countries. Countries with early and high uptake rates of effective screening have exhibited major declines in CRC incidence and mortality, in contrast to most other countries. Finally, increasing evidence shows that the prognosis and quality of life of CRC patients can be substantially improved by tertiary prevention measures, such as the administration of low-dose aspirin and the promotion of physical activity. [ABSTRACT FROM AUTHOR]

Background Urinary 8‐isoprostane is an established biomarker for lipid peroxidation. However, the association between its pre-diagnostic levels and cancer incidence has rarely been evaluated. Methods 8793 older adults from the German ESTHER cohort were followed up for cancer incidence by cancer registry data. A directed acyclic graph was utilized to identify potential confounders. Multivariate Cox regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). Results During 14-year follow-up, 1540 incident cancer cases, including 207 lung, 196 colorectal, 218 breast and 245 prostate cancer cases were detected. 8-isoprostane concentrations were positively associated with lung cancer, but not with cancer at the other sites. The HR (95% CI) for the association with lung cancer was 1.61 (1.10, 2.34) for comparison of the top with bottom tertile in total population. The association of 8-isoprostane levels with lung cancer persisted after the adjustment for smoking and other potential confounders and was multiplicative to the effect of smoking. However, 8-isoprostane levels did not improve lung cancer prediction when added to a model containing age, sex and smoking. A protective association of increasing 8-isoprostane levels was observed for prostate cancer incidence but this association was only statistically significant among current smokers. Discussion Our findings suggest that lipid peroxidation is involved in the development of lung cancer. However, high oxidative stress may be a protective factor for prostate cancer, especially among current smokers. [ABSTRACT FROM AUTHOR]

Background: Evidence of an inverse association between serum vitamin D and mortality from epidemiological studies has prompted efforts to reduce mortality by vitamin D supplementation, either in targeted interventions for people with vitamin D insufficiency or deficiency, or in untargeted interventions regardless of baseline vitamin D status.Objective: We aimed to assess the expected impact of the 2 different approaches on effect sizes and power of intervention studies.Methods: Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were measured in 9579 participants aged 50-75 y in the German Epidemiologische Studie zu Chancen der Verhütung, Früherkennung und optimierten Therapie chronischer Erkrankungen in der älteren Bevölkerung (ESTHER) study who were followed for mortality for a median of 12.4 y. We estimated adjusted HRs of mortality from all causes, cardiovascular disease, and cancer for defined increases in serum 25(OH)D by Cox regression, both across the full range of 25(OH)D concentrations and for those with vitamin D insufficiency [30 nmol/L ≤ 25(OH)D < 50 nmol/L] or deficiency [25(OH)D <30 nmol/L] only, and we calculated the power of intervention studies achieving those effect sizes.Results: An inverse association between serum 25(OH)D and mortality was observed only for participants with vitamin D insufficiency or deficiency and was strongest for the latter. Accordingly, the expected effects were much stronger and the expected power was much higher for interventions that targeted these groups than for untargeted interventions. For example, a targeted intervention study with 10,000 older adults (age 50-75 y) with serum 25(OH)D <50 nmol/L that increases serum 25(OH)D concentrations by 20 nmol/L in the intervention group (n = 5000) would be expected to yield a 26% reduction of all-cause mortality that could be detected with 89% power within 5 y of follow-up compared with a 10% mortality reduction and 20% power in an untargeted intervention study of the same size.Conclusions: Vitamin D supplementation trials aimed at reducing mortality in older adults have much higher power when focused on those with low serum 25(OH)D concentrations. [ABSTRACT FROM AUTHOR]

Link between obesity and early onset colorectal cancers: Importance of accounting for BMI trajectories in early life. All studies included in our review considered body mass index (BMI) at late adolescence, young or middle adulthood, i.e., at ages during which BMI trajectories are rather stable ([[3]]). Nevertheless, we agree that timing of BMI measurements and BMI trajectories are crucial factors to be considered in the study of the role of overweight and obesity for colorectal cancer (CRC), including early-onset colorectal cancer (EOCRC). [Extracted from the article]

Background: Colorectal cancer (CRC) is the third most common cancer worldwide. If detected at an early stage, prognosis is good. Despite increasing evidence for the benefits of implemented screening programs, such as screening colonoscopy, compliance is rather low. Hence there is demand for non-invasive tests for the early detection of CRC with high acceptance in population-wide screening. The objective of this study was to identify and evaluate leukocyte DNA methylation patterns as a potential biomarker for early detection of CRC. Methods: Blood samples of patients scheduled for a screening colonoscopy were collected before the procedure. Additionally, blood samples from CRC cases recruited in a clinical setting were collected. DNA was extracted from leukocytes, and DNA methylation was measured with the Infinium 450K BeadChip. In total, 46 CRC cases and 140 controls from the screening setting and 93 CRC cases from the clinical setting were measured. Results: An epigenome-wide discovery revealed two CpG sites in the promoter region of KIAA1549L that were significantly differentially methylated between cases and controls. A third marker in the body region of BCL2 was discovered in a candidate approach testing biomarkers reported in the literature. Logistic regression models built on these three markers yielded an optimism-corrected c-statistic of 0.69 in the screening setting and 0.73 in the clinical setting. Conclusions: Although diagnostic performance of the DNA methylation signature identified in this first epigenomewide association study of leukocyte DNA methylation with CRC in a screening setting is not competitive with established screening tests, the identified markers may contribute to multimarker panels for early detection of CRC. [ABSTRACT FROM AUTHOR]

Background: The proportion of cases notified by death certificate only (DCO) is a commonly used data quality indicator in studies comparing cancer survival across regions and over time. We aimed to assess dependence of DCO proportions on the age structure of cancer patients. Methods: Using data from a national cancer survival study in Germany, we determined age specific and overall (crude) DCO proportions for 24 common forms of cancer. We then derived overall (crude) DCO proportions expected in case of shifts of the age distribution of the cancer populations by 5 and 10 years, respectively, assuming age specific DCO proportions to remain constant. Results: Median DCO proportions across the 24 cancers were 2.4, 3.7, 5.5, 8.5 and 23.9% in age groups 15-44, 45-54, 55-64, 65-74, and 75+, respectively. A decrease of ages by 5 and 10 years resulted in decreases of cancer specific crude DCO proportions ranging from 0.4 to 4.8 and from 0.7 to 8.6 percent units, respectively. Conversely, an increase of ages by 5 and 10 years led to increases of cancer specific crude DCO proportions ranging from 0.8 to 4.8 and from 1.8 to 9.6 percent units, respectively. These changes were of similar magnitude (but in opposite direction) as changes in crude 5-year relative survival resulting from the same shifts in age distribution. Conclusions: The age structure of cancer patient populations has a substantial impact on DCO proportions. DCO proportions should therefore be age adjusted in comparative studies on cancer survival across regions and over time. [ABSTRACT FROM AUTHOR]

Background: The free radical/oxidative stress theory of ageing has received considerable attention, but the evidence on the association of oxidative stress markers with mortality is sparse.Methods: We measured derivatives of reactive oxygen metabolite (D-ROM) levels as a proxy for the reactive oxygen species concentration and total thiol levels (TTL) as a proxy for the redox control status in 10,622 men and women (age range, 45-85 years), from population-based cohorts from Germany, Poland, Czech Republic, and Lithuania, of whom 1,702 died during follow-up.Results: Both oxidative stress markers were significantly associated with all-cause mortality independently from established risk factors (including inflammation) and from each other in all cohorts. Regarding cause-specific mortality, compared to low D-ROM levels (≤ 340 Carr U), very high D-ROM levels (>500 Carr U) were strongly associated with both cardiovascular (relative risk (RR), 5.09; 95 % CI, 2.67-9.69) and cancer mortality (RR, 4.34; 95 % CI, 2.31-8.16). TTL was only associated with CVD mortality (RR, 1.30; 95 % CI, 1.15-1.48, for one-standard-deviation-decrease). The strength of the association of TTL with CVD mortality increased with age of the participants (RR for one-standard-deviation-decrease in those aged 70-85 years was 1.65; 95 % CI, 1.22-2.24).Conclusions: In these four population-based cohort studies from Central and Eastern Europe, the oxidative stress serum markers D-ROM and TTL were independently and strongly associated with all-cause and CVD mortality. In addition, D-ROM levels were also strongly associated with cancer mortality. This study provides epidemiological evidence supporting the free radical/oxidative stress theory of ageing and suggests that d-ROMs and TTL are useful oxidative stress markers associated with premature mortality. [ABSTRACT FROM AUTHOR]

Aim Endoscopy based screening programmes for colorectal cancer (CRC) are being implemented in an increasing number of countries. In Germany, screening colonoscopy at age 55 or older has been offered since the end of 2002. We aimed to estimate the long-term impact of this offer on CRC prevention. Methods We estimated numbers of prevented CRC cases by expected age and year of their (prevented) occurrence over four decades (2005–2045) by four state Markov models (non-advanced adenoma, advanced adenoma, preclinical CRC, clinically manifest CRC). Estimates are based on screening colonoscopies reported to the German screening colonoscopy registry in 2003–2012 ( N = 4,407,971), transition rates between the four states and general population mortality rates. Results Numbers of prevented clinically manifest CRC cases are projected to increase from <100 in 2005 to approximately 6500 in 2015, 12,600 in 2025, 15,400 in 2035 and 16,000 in 2045, compared to approximately 58,000 incident cases observed in 2003. The annual number of prevented cases is expected to be higher among men than among women and to strongly vary by age. The vast majority of prevented cases would have occurred at age 75 or older. Conclusions Despite modest participation rates, the German screening colonoscopy programme will lead to substantial reductions in the CRC burden. The reductions will be fully disclosed in the long run only and predominantly affect numbers of incident cases above 75 years of age. Screening offers would need to start at younger ages in order to achieve more effective CRC prevention at younger ages. [ABSTRACT FROM AUTHOR]

Background: Studies on the implementation of Clinical Practice Guidelines (CPG) and particularly its effect on breast cancer (BRC) survival on a population-level are scant. This population-based high resolution study from Germany aims at providing data on the usage of BRC treatment, the extent of adherence to CPG and, as a novelty, survival of BRC patients according to major recommended treatment options. Methods: Data from the Saarland Cancer Registry including women diagnosed with invasive BRC without distant metastasis and followed up between 2000 and 2009 were used. Provision of cancer care according to major treatment options is presented by age, clinical subtypes of BRC, and over time. Conventional and modeled period analysis was used to derive estimates of most up-to-date 5-year relative survival (RS) and the effect of non-adherence to CPG on relative excess risk of death (RER). Results: The study revealed increasing guideline adherence, with high levels already seen for local treatment (e.g. 67% of the BRC patients in 2008/09 received breast conserving surgery), and substantial progress since the millennium change with regard to sentinel node dissection (SND) and adjuvant systemic treatments (e.g. SND and chemotherapy provided to 62% of all patients and 79% of the patients with nodal positive or hormone receptor negative BRC in 2008/09, respectively). It further demonstrated increased cancer related mortality among patients without guideline compliant cancer treatment (e.g. patients with nodal positive and hormone receptor negative BRC who were not treated with chemotherapy had a 5-year RS of 29% (RER: 2.89, 95% CI: 1.46-5.71) compared to 54% for patients obtaining chemotherapy). Conclusions: This study provides data on the implementation of CPG in a highly developed European country and extends available population-based survival data of BRC patients and may provide evidence of increased cancer related excess mortality, if BRC patients do not receive guideline compatible treatment. [ABSTRACT FROM AUTHOR]

The article provides information on colorectal cancer. It discusses its incidence and mortality, prognosis of colorectal cancer patients, its risk factors and preventive measures, its histopathological classification, its molecular pathogenesis, the forms of hereditary colorectal cancers and its treatment.

OBJECTIVES:Randomized trials have shown that annual or biannual screening by guaiac-based fecal occult blood tests (gFOBTs) reduces colorectal cancer (CRC) mortality. Few clinical studies have evaluated diagnostic performance of gFOBT through validation by colonoscopy in all participants. We aimed for a comprehensive evaluation of diagnostic performance of gFOBT by age and sex under routine screening conditions.METHODS:Our analysis is based on 20,884 colonoscopies following up a positive gFOBT and 182,956 primary screening colonoscopies documented in a state-wide quality assurance program in Bavaria, Germany, in 2007-2009. Positive likelihood ratios (LR+), which represent an integrative measure of diagnostic performance, were derived, by age groups (55-59, 60-64, 65-69, 70-74 years) and sex, from a joint and comparative analysis of prevalences of colorectal neoplasms in both groups.RESULTS:Overall LR+ (95% confidence intervals) were 1.11 (1.06-1.15), 1.80 (1.72-1.88), and 5.04 (4.64-5.47) for non-advanced adenoma, advanced adenoma, and cancer, respectively. Assuming a specificity of gFOBT of 95.2%, as recently observed in a German study among 2,235 participants of screening colonoscopy, these LR+ would translate to sensitivities of 5.3%, 8.6%, and 24.2% for the three outcomes, respectively. Diagnostic performance was similarly poor among women and men and across age groups.CONCLUSIONS:The performance of gFOBT under routine screening conditions is even worse than previously estimated from clinical studies. In routine screening application, gFOBTs are expected to miss more than 9 out of 10 advanced adenomas and 3 out of 4 cancers. These results underline the need and the potential for better noninvasive CRC screening tests. [ABSTRACT FROM AUTHOR]

Objectives: A common approach in the evaluation of screening for colorectal cancer (CRC) is comparing observed numbers of CRC deaths in screening participants with expected numbers derived from CRC mortality in the general population. We aimed to illustrate and quantify an often-overlooked bias that may occur in such studies if CRC mortality in the general population is not restricted by the date of diagnosis (whereas screening participants by definition do not have a prior CRC diagnosis). Study Design and Setting: We illustrate and quantify the expected bias using cancer registry data from the United States. Results: Unless an incidence-based mortality approach is used, expected numbers of CRC deaths in screening cohorts (and hence estimated screening effects) are substantially overestimated. Overestimation of expected CRC deaths is most severe (more than fivefold) during the first year of follow-up and rapidly decreases in the subsequent years. Nevertheless, overestimation of 5- and 10-year cumulative numbers of expected CRC deaths is still as high as 60-70% and 20-30%, respectively. Substantial bias even persists if the initial years of follow-up are excluded from the analyses. Conclusion: Careful restriction of expected CRC deaths by an incidence-based mortality approach is indispensable for deriving valid screening effect estimates. [ABSTRACT FROM AUTHOR]

Objectives: Although randomized controlled trials (RCTs) are considered the most valid approach to evaluate screening effects, they also face a number of methodological challenges, including nonadherence and contamination. We aimed to quantify their potential impact in RCTs evaluating endoscopic screening for colorectal cancer (CRC). Study Design and Setting: We carried out model calculations using plausible levels of nonadherence and contamination. Results: Assuming medium values of adherence (70%) and contamination, that is, use of lower gastrointestinal endoscopy other than the one offered for screening (30%), true reductions in CRC incidence or mortality of 70%, 50%, or 30% would be expected to be attenuated to reductions of 43%, 29%, and 16%, respectively, in intention-to-screen analyses. In case of low levels of adherence (50%) and high but realistic levels of contamination (50%), even more severe attenuation of screening effects to estimated reductions of 27%, 17%, and 9% would be expected. The estimates are only slightly modified in sensitivity analyses, additionally allowing for differential adherence and contamination according to CRC risk. Conclusion: In the era of widespread endoscopy use even outside the screening programs, RCTs may strongly underestimate the effects of CRC screening. Additional analyses accounting for nonadherence and contamination are crucial for disclosing the true screening effects. [ABSTRACT FROM AUTHOR]

Abstract: There is increasing evidence that faecal immunochemical tests (FITs) for haemoglobin offer a number of advantages over traditional guaiac based faecal occult blood tests (gFOBTs). However, evidence on diagnostic performance from direct comparisons with colonoscopy findings in all participants in the average risk population is still sparse. We aimed for a head-to-head comparison of three quantitative FITs with a gFOBT among participants of the German screening colonoscopy programme. Pre-colonoscopy stool samples and colonoscopy reports were obtained from 2235 participants of screening colonoscopy in 2005–2009. To enhance comparability of diagnostic performance of the various tests, we assessed sensitivity, specificity, predictive values and likelihood ratios of FITs after adjusting the FIT cut-off haemoglobin (Hb) concentrations in such a way that FIT positivity rates equalled the positivity rate of the gFOBT. Colorectal cancer, advanced adenomas and other adenomas were found in 15 (0.7%), 207 (9.3%) and 398 (17.8%) participants. The gFOBT was positive in 111 (5.0%) participants, with sensitivities (specificities) for detecting colorectal cancer, any advanced neoplasm or any neoplasm of 33.3% (95.2%), 8.6% (95.4%) and 5.5% (95.2%). At the same positivity rate, all three FITs outperformed the gFOBT in all indicators. In particular, all sensitivities of FITs were approximately two to three times higher at increased levels of specificity. All differences were statistically significant, except for some of the performance indicators for colorectal cancer. In conclusion, FITs can detect much larger proportions of colorectal neoplasms even if their cut-offs are set to levels that ensure equally low positivity rates as gFOBT. [Copyright &y& Elsevier]

Abstract: Period analysis is increasingly employed in analyses of long-term survival of patients with chronic diseases such as cancer, as it derives more up-to-date survival estimates than traditional cohort based approaches. It has recently been extended with regression modelling using generalized linear models, which increases the precision of the survival estimates and enables to assess and account for effects of additional covariates. This paper provides a detailed presentation how model based period analysis may be used to derive population-based absolute and relative survival estimates using the freely available R language and statistical environment and already available R programs for period analysis. After an introduction of the underlying regression model and a description of the software tools we provide a step-by-step implementation of two regression models in R and illustrate how estimates and a test for trend over time in relative survival may be derived using data from a population based cancer registry. [Copyright &y& Elsevier]

Abstract: Background : The proportion of cases notified by death certificate only (DCO) is a commonly used criterion to judge completeness of cancer registration even though it is affected by additional factors, particularly during initial years of newly established registries. Methods : Based on cancer registry data from the United States, we provide model calculations to demonstrate the magnitude and time course of the impact of the following mechanisms on DCO proportions of “young” registries: registration of cancer deaths from patients diagnosed prior to the registration period and delayed registration by death certificate of patients diagnosed but not reported after initiation of registration. Results : DCO proportions of up to ⩾30% can be expected from deaths of previously diagnosed patients during the first year of registration. Although this proportion is expected to gradually diminish over subsequent years, DCO proportions may be dominated for several years by this source, which may still be relevant after 10 or more years of cancer registration for cancers with relatively large proportions of late deaths. Otherwise, however, underreporting during patients’ lifetime is expected to become the predominant source of DCO proportions in the long run. Conclusions : Our results may guide interpretation of DCO proportions of relatively “young” cancer registries. [Copyright &y& Elsevier]

Objectives: In the evaluation of cancer screening tests, cancer-free controls are often matched to cancer cases on factors such as sex and age. We assessed the potential merits and pitfalls of such matching using an example from colorectal cancer (CRC) screening. Study Design and Setting: We compared sex and age distribution of CRC cases and cancer-free people undergoing screening colonoscopy in Germany in 2006 and 2007. We assessed specificity by sex and age of two immunochemical fecal occult blood tests (iFOBTs) in a study among screening colonoscopy participants conducted in the same years, and we assessed the expected impact of matching by sex and age on the validity of specificity estimates at various cut points. Results: In the screening colonoscopy program, the proportion of men and mean age were 59.6% and 68.6 years among 10,324 CRC patients compared with 45.6% and 64.7 years, respectively, among 997,490 cancer-free participants. The specificity of the iFOBTs was higher among women than among men and decreased with age. Matching of cancer-free controls by age and sex would have led to the underestimation of specificity at all cut points assessed. Conclusion: In the evaluation of cancer screening tests, matching of controls may lead to biased estimates of specificity. [ABSTRACT FROM AUTHOR]

Objective The risk of colorectal cancer after a previous negative colonoscopy is very low. Nevertheless, interval cancers occur. We aimed to assess the characteristics and predictors of interval cancers after negative colonoscopy. Methods A population-based case-control study was conducted in Southern Germany in 2003e7. Sociodemographic and tumour characteristics were compared among 78 patients with interval cancers occurring 1e10 years after a negative colonoscopy and 433 colorectal cancers detected at screening. In addition, the indication for the preceding negative colonoscopy and its completeness were compared between patients with interval cancers and 515 controls with a preceding negative colonoscopy. Results 56.4% of interval cancers occurred among women compared with 33.7% of cases detected by screening (p=0.0001). After adjustment for covariates, female sex (OR 2.28, 95% CI 1.35 to 3.83) and location in the caecum or ascending colon (OR 1.98, 95% CI 1.17 to 3.35) were independently associated with occurrence of interval cancers. The preceding negative colonoscopy was more commonly conducted because of a positive faecal occult blood test (26.0% vs 12.9%, p¼0.009) and was more often incomplete (caecum not reached: 18.1% vs 6.7%, p=0.001) among interval cancer cases than among controls. Characteristics of the preceding negative colonoscopy strongly and independently associated with occurrence of interval cancers were follow-up of a positive faecal occult blood test among men (OR 5.49, 95% CI 2.10 to 14.35) and incompleteness among women (OR 4.38, 95% CI 1.69 to 11.30). Conclusions The observed patterns suggest that a substantial proportion of interval cancers are due to neoplasms missed at colonoscopy and are potentially preventable by enhanced performance of colonoscopy. [ABSTRACT FROM AUTHOR]

Background: Studies have identified characteristics of adenomas detected on colonoscopy to be predictive of adenoma recurrence. Objective: To assess the role of both colonoscopy-related factors and polyp characteristics on the risk for colorectal cancer after colonoscopic polyp detection. Design: Population-based case-control study (3148 case partici-pants and 3274 control participants). Setting: Rhine-Neckar region of Germany. Patients: Case and control participants with physician-validated detection of polyps (other than hyperplastic polyps) at a previous colonoscopy in the past 10 years. Measurements: Detailed history and results of previous colonosco-pies were obtained through interviews and medical records. Case and control participants were compared according to colonoscopy-related factors (incompleteness, poor bowel preparation, incomplete removal of all polyps, and no surveillance colonoscopy within 5 years) and polyp characteristics (≥1 cm, villous components or high-grade dysplasia, ≥3 polyps, and ≥1 proximal polyp). Odds ratios (ORs) and attributable fractions were derived by using mul-tiple logistic regression and the Levin formula. Results: 155 case participants and 260 control participants with physician-validated polyp detection in the past 10 years were iden-tified. The following characteristics were significantly more common among case participants than among control participants: not all polyps completely removed (29.0% vs. 9.6%; OR, 3.73 [95% Cl, 2.11 to 6.60]), no surveillance colonoscopy within 5 years (26.5% vs. 11.5%; OR, 2.96 [Cl, 1.70 to 5.16]), and detection of 3 or more polyps (14.2% vs. 7.3%; OR, 2.21 [Cl, 1.07 to 4.54]). Odds ratios ranged from 1.12 to 1.42 and CIs included 1.00 for all other variables. Overall, 41.1% and 21.7% of cancer cases were statis-tically attributable to colonoscopy-related factors and polyp charac-teristics, respectively. Limitation: This was an observational study with potential for residual confounding and selection bias. Conclusion: Colonoscopy-related factors are more important than polyp characteristics for stratification of colorectal cancer risk after colonoscopic polyp detection in the community setting. Primary Funding Source: German Research Council and German Federal Ministry of Education and Research. [ABSTRACT FROM AUTHOR]

Objective High serum calcium and phosphate levels have been linked to cardiovascular diseases and all-cause mortality but evidence from longitudinal studies is scarce, especially among patients with pre-existing coronary heart disease. The association between baseline calcium and phosphate and prognosis was examined in a cohort study of patients with stable coronary heart disease. Methods Serum calcium and phosphate were measured in a cohort of initially 1206 patients undergoing a 3 week rehabilitation programme after an acute cardiovascular event and subsequently being followed-up for 8 years. Multivariate Cox regression was employed to assess the association of quartiles and continuous levels of calcium and phosphate with secondary cardiovascular events and all-cause mortality. Results No significant risk elevations were observed for secondary cardiovascular event incidence in models adjusted for a variety of potential confounders. High calcium levels, however, were strongly associated with mortality risk in adjusted models (HRQ4vsQ1=2.39 (1.22 to 4.66)). In additional multivariable analyses, the calcium/albumin ratio was predictive for all-cause mortality (HRQ4vsQ1=2.66 (1.35 to 5.22)) and marginally predictive for cardiovascular event incidence (HRQ4vsQ1=1.74 (1.00 to 3.05)). Conclusions Calcium and the ratio of calcium with albumin, its major binding protein, were strongly associated with all-cause mortality among patients with coronary heart disease. The underlying mechanisms and the clinical implications of these findings deserve further study. [ABSTRACT FROM AUTHOR]

Abstract: Background: Survival studies using data from population-based cancer registries allow assessing effectiveness of cancer care on a population level. However, population-based cancer registries differ in the proportion of cases first notified by death certificate, as well as in the efforts to trace back such death certificate notifications (DCN). We aimed to assess the impact of such trace back on population-based cancer survival estimates. Materials and methods: In this study from the population-based Saarland Cancer Registry (Germany) we investigated the survival experience of successfully traced back DCN cases from 1994 to 2003. Five-year relative survival of patients with DCN cancers and the effect of trace back on population-based 5-year relative survival estimates were analysed by age and tumour site. Results: Twelve percent of all cancers were DCN and such cases occurred most often amongst sites with poor prognosis and amongst elderly patients. Approximately half of DCN cases could be successfully traced back. Five-year relative survival of patients with DCN cancers with trace back was 2%. The inclusion of DCN cancers with additional registrations reduced the 5-year relative survival estimate for all cancers combined by 4% points. Reductions were stronger for older patients and highly fatal cancers. Conclusions: Trace back results in increased inclusion of patients with very poor prognosis. Varying extent of trace back across registries may compromise comparability of cancer survival estimates and should be taken into account in comparative cancer survival studies. [Copyright &y& Elsevier]

Background: Studies have revealed both higher cancer survival in the US than in Germany and substantial improvement of cancer survival in the past in these countries. This population-based study aims at comparing most recent 5-year relative survival of breast cancer patients and preceding trends in both countries. Methods: Women with a first invasive breast cancer diagnosed and followed up between 1988 and 2008 from Germany and the US (utilizing data from the Saarland Cancer Registry and the Surveillance, Epidemiology, and End Results Program, respectively) were included. Period analysis was used to derive most up-to-date 5-year relative survival and preceding survival trends according to age and stage. Results: Since 1993, age standardized relative survival has steadily improved in Germany and the US to 83% and 88%, respectively. In the period 2005-08, relative survival of localized cancer was above 97% in both countries, and 79% and 83% for locally/regionally spread breast cancer, respectively. Prognosis of metastasized disease has remained very poor overall, with improvement essentially being restricted to younger patients. The proportion of patients diagnosed with localized breast cancer was consistently higher in the US. If adjusted for stage, the differences in relative survival between both countries diminished over time and eventually disappeared. Conclusions: Similar survival is now observed in both countries for patients below the age of 70 years, but in Germany survival is still much lower for elderly patients. The observed trends point to treatment advances as a major cause for improved survival. However, substantial differences in mammography usage existed between both countries and might probably also account for the observed differences (to a lesser extent, also differences inhealth care systems, and delivery of cancer care). Encouraging, survival of breast cancer patients has improved in Germany to a much greater extent than in the US, albeit the persisting survival gap for elderly patients in Germany requires particular attention by researchers, public health authorities, and clinicians. [ABSTRACT FROM AUTHOR]

The sojourn time of preclinical colorectal cancer is a critical parameter in modeling effectiveness and cost-effectiveness of colorectal cancer screening. For ethical reasons, it cannot be observed directly, and available estimates are based mostly on relatively small historic data sets that do not include differentiation by age and sex. The authors derived sex- and age-specific estimates (age groups: 55–59, 60–64, 65–69, 70–74, 75–79, and ≥80 years) of mean sojourn time, combining data from the German national screening colonoscopy registry (based on 1.88 million records) and data from population-based cancer registries (population base: 37.9 million people) for the years 2003–2006. Estimates of mean sojourn time were similar for both sexes and all age groups and ranged from 4.5 years (95% confidence interval: 4.1, 4.8) to 5.8 years (95% confidence interval: 5.3, 6.3) for the subgroups assessed. Sensitivity analyses indicated that mean sojourn time might be approximately 1.5 years longer if colorectal cancer prevalence in nonparticipants of screening colonoscopy is 20% lower than prevalence in participants or 1 year shorter if it exceeds the prevalence in participants by 20%. This study provides, for the first time, precise estimates of sojourn time by age and sex, and it suggests that sojourn times are remarkably consistent across age groups and in both sexes. [ABSTRACT FROM PUBLISHER]

Background: Helicobacter pylori infection is a key risk factor for a variety of gastrointestinal diseases. About half of the world population is infected. Most infections are acquired early in childhood, but the occurrence of new infections among adults has also been suggested. Methods: We review epidemiological studies providing estimates of incidence of H. pylori infection among adults and evaluate to what extent incidence estimates might have been affected by measurement error of infection status. Results: Thirty-two studies could be included in the review. Annual incidence was lower than 1.0 % in 17 studies; no correlation between length of follow-up and cumulative incidence was observed. Apparent cumulative incidences of the magnitudes observed in most studies would be expected, because of less than perfect sensitivity and specificity of the diagnostic tests, even in the absence of any true new infections. Conclusion /Impact: Apparent incidence rates of H. pylori infection among adults in Western populations should be interpreted with utmost caution. [ABSTRACT FROM AUTHOR]

Background: Colonoscopy with detection and removal of adenomas is considered a powerful tool to reduce colorectal cancer (CRC) incidence. However, the degree of protection achievable in a population setting with high-quality colonoscopy resources remains to be quantified. Objective: To assess the association between previous colonoscopy and risk for CRC. Design: Population-based case-control study. Setting: Rhine-Neckar region of Germany. Patients: A total of 1688 case patients with colorectal cancer and 1932 control participants aged 50 years or older. Measurements: A detailed lifetime history of CRC risk factors and preventive factors, including history and results of previous colonoscopies, and of medical data obtained by self-reports and medical records. Odds ratios of CRC associated with colonoscopy in the preceding 10 years were estimated, after adjustment for sex, age, education level, participation in a general health screening examination, family history of CRC, smoking status, body mass index, and use of nonsteroidal anti-inflammatory drugs or hormone replacement therapy. Results: Overall, colonoscopy in the preceding 10 years was associated with 77% lower risk for CRC. Adjusted odds ratios for any CRC, right-sided CRC, and left-sided CRC were 0.23 (95% CI, 0.19 to 0.27), 0.44 (CI, 0.35 to 0.55), and 0.16 (CI, 0.12 to 0.20), respectively. Strong risk reduction was observed for all cancer stages and all ages, except for right-sided cancer in persons aged 50 to 59 years. Risk reduction increased over the years in both the right and the left colon. Limitation: The study was observational, with potential for residual confounding and selection bias. Conclusion: Colonoscopy with polypectomy can be associated with strongly reduced risk for CRC in the population setting. Aside from strong risk reduction with respect to left-sided CRC, risk reduction of more than 50% was also seen for right-sided colon cancer. Primary Funding Source: German Research Council and German Federal Ministry of Education and Research. [ABSTRACT FROM AUTHOR]

The article presents information on a study which investigated the relationship between low-dose aspirin use and the performance of immunochemical fecal occult blood tests (iFOBT) in patients being subjected to colorectal cancer screening. The diagnostic study conducted from 2005 through 2009 recruited 233 regular users of low-dose aspirin and 1746 who never used low-dose aspirin from internal medicine and gastroenterology practices in southern Germany. It cites the main outcome measures of the research study. A discussion on the research findings is detailed.

OBJECTIVES:Immunological and guaiac-based fecal occult blood tests (iFOBTs and gFOBTs) are widely used for early detection of colorectal cancer (CRC). We aimed to assess potential sex differences in performance of iFOBTs and gFOBT in the screening setting.METHODS:The sensitivity, specificity, and positive and negative predictive values for detection of advanced colorectal neoplasms (CRC or advanced adenoma) were assessed by sex for a range of cutpoints of a quantitative iFOBT (RIDASCREEN Hemoglobin), six qualitative iFOBTs, and a gFOBT (HemOccult) among 1,157 male and 1,167 female participants of the German screening colonoscopy program (mean age: 63.0 and 62.0 years, respectively).RESULTS:The prevalence of advanced colorectal neoplasms was much higher among men (13.5%) than among women (7.5%). At any cutpoint of the quantitative iFOBT, and for all qualitative iFOBTs and the gFOBT, the sensitivity and positive predictive value were substantially higher, and specificity and negative predictive value were substantially lower among men than among women. At the cutpoint of 2 μg/g stool given by the manufacturer of the quantitative iFOBT, sensitivity, specificity, and the positive and negative predictive values were 47.6, 85.0, 33.0, and 91.3% among men, and 30.7, 89.5, 19.3, and 94.1% among women (P value for sex differences 0.001, 0.002, 0.004, and 0.019, respectively). Sex differences in predictive values were mostly explained by sex differences in the prevalence of advanced colorectal neoplasms.CONCLUSIONS:There are major sex differences in the performance of fecal occult blood testing, which might require careful attention in the interpretation of test results, and in the design, modeling, and evaluation of CRC screening strategies. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Chronic kidney disease (CKD) increases risk of coronary heart disease (CHD), but the impact of using different equations for estimating kidney function on CHD is not clear yet. This study described the prognostic value of CKD as defined by various creatinine- (Cr-eGFR) and cystatin C-based estimating (Cys-eGFR) equations and their combinations on subsequent cardiovascular disease (CVD) events in patients with CHD. Design: Cohort study. Setting: Patients with coronary heart disease in in-patient rehabilitation and long-term follow-up (mean 63.4 months). Subjects: 1050 patients with coronary heart disease aged 30–70 years at baseline. Methods: CKD was defined as eGFR<60mL/min/1.73m2 (CKD stages 3–5) estimated by three Cr-eGFR equations (Cockroft–Gault equation adjusted for body surface area (CG/BSA), Modification of Diet in Renal Disease Study (MDRD) equation, CKD-EPIcrea) and by two Cys-eGFR equations (Arnal-Dade equation, CKD-EPIcys) and a combination. The primary endpoint of our study was subsequent CVD events. Results: During follow-up 118 patients (11.2%) experienced the outcome of our study. CKD assessed by the CG/BSA, MDRD, and CKD-EPIcrea equations showed no statistically significant association with subsequent CVD events after adjustment for multiple covariates (hazard ratio (HR) 1.45 [95% CI, 0.81–2.59], HR 1.47 [95% CI, 0.84–2.60], and HR 1.31 [95% CI, 0.72–2.83], respectively). By contrast, the Cys-eGFR equations were much stronger associated with subsequent CVD endpoints (Arnal-Dade: HR, 2.01 [95% CI, 1.34–3.04]; CKD-EPIcys HR, 2.22 [95% CI, 1.46–3.37]). The CKD-EPIcys also provided the highest area under the curve value. Conclusion: Our study shows that prevalent CKD is an independent risk factor for subsequent CVD in patients with prevalent CHD and implies that Cys-eGFR equations show a better clinical utility compared to the Cr-eGFR equations. [Copyright &y& Elsevier]

Background: Prevalence of advanced colorectal neoplasms increases with age and is higher among men than women. Crosssectional analyses estimated that men reach an equivalent prevalence at a much younger age than women. However, crosssectional estimates may be confounded by birth cohort effects. Objective: To estimate age and cohort effects in advanced colorectal neoplasms and to adjust risk-advancement periods for men compared with women for birth cohort effects. Design: Age-cohort analyses. Setting: German screening colonoscopy program, 2003 to 2007. Participants: 2 185 153 participants aged 55 to 75 years. Measurements: Sex- and age-specific prevalence of colorectal cancer (CRC) and advanced neoplasms (CRC or advanced adenoma) were plotted with and without stratification by birth cohort. Risk advancement periods with 95% CI for men compared with women were estimated from log-binomial regression models with and without cross-sectional analysis adjustment for birth cohort effects. Results: Overall, 17 196 participants (0.8%) had CRC and 152 429 (7.0%) had any advanced neoplasm. Age-specific prevalence was higher in men than in women and in later birth cohorts. The apparent modest increase in prevalence by age in cross-sectional analysis was much steeper after birth cohort effects were controlled for. In cross-sectional analysis, risk-advancement periods (95% CI) for men compared with women were 8.4 years (CI, 7.7 to 9.0 years) and 16.1 years (CI, 15.8 to 16.5 years) for CRC and any advanced neoplasm, respectively, and 3.4 years (CI, 2.6 to 4.3 years) and 6.9 years (CI, 6.4 to 7.4 years) after controlling for birth cohort effects. Limitation: Information on covariates that could explain cohort effects was lacking. Conclusion: In this population, strong cohort effects reduced age gradients in advanced colorectal neoplasms and inflated riskadvancement periods for men compared with women, but major risk advancement persisted, even after birth cohort effects were controlled for. [ABSTRACT FROM AUTHOR]

Background: Colonoscopy is used for early detection and prevention of colorectal cancer, but evidence on the magnitude of overall protection and protection according to anatomical site through colonoscopy performed in the community setting is sparse. We assessed whether receiving a colonoscopy in the preceding 10-year period, compared with no colonoscopy, was associated with prevalence of advanced colorectal neoplasms (defined as cancers or advanced adenomas) at various anatomical sites. [ABSTRACT FROM PUBLISHER]

Abstract: Within the past 10–15 years, major advances in therapy have strongly improved prognosis of patients with chronic myelocytic leukaemia (CML). We estimated trends in 5- and 10-year relative survival of patients developing CML after a previous malignancy in the United States from 1990–1994 to 2000–2004. Period analysis was employed to disclose recent developments with minimum delay. Overall, 5- and 10-year relative survival increased from 17.6% to 37.7% (p <0.0001) and from 7.6% to 23.8% (p <0.0001), respectively. Improvements were particularly strong in younger age groups. Prognosis of CML patients with previous malignancy no longer lags behind prognosis of patients with primary CML. [Copyright &y& Elsevier]

Abstract: In late 2002, colonoscopy was introduced as a primary screening tool for colorectal cancer (CRC) in Germany. We aimed to estimate the expected reduction in case numbers and incidence of CRC between 2003 and 2010 by detection and removal of advanced adenomas. Data from 1,875,708 women and men included in the national screening colonoscopy database were combined with estimates of transition rates of advanced adenomas and with national population projections. Despite relatively low screening participation, incident CRC cases are expected to be reduced by more than 15,000 between 2003 and 2010. The impact is expected to be largest in age groups 55–59, 60–64 and 65–69 in whom total case numbers in 2010 are expected to be reduced by 13%, 19% and 14% among women, and by 11%, 15% and 12%, respectively, among men. Our results forecast a major rapid reduction of the CRC burden in Germany by screening colonoscopy. [Copyright &y& Elsevier]

Abstract: Period analysis has been shown to provide more up-to-date estimates of long-term cancer survival rates than traditional cohort-based analysis. Here, we provide detailed period estimates of 5- and 10-year relative survival by cancer site, country, sex and age for calendar years 2000–2002. In addition, pan-European estimates of 1-, 5- and 10-year relative survival are provided. Overall, survival estimates were mostly higher than previously available cohort estimates. For most cancer sites, survival in countries from Northern Europe, Central Europe and Southern Europe was substantially higher than in the United Kingdom and Ireland and in countries from Eastern Europe. Furthermore, relative survival was also better in female than in male patients and decreased with age for most cancer sites. [Copyright &y& Elsevier]

OBJECTIVES: To review and combine the best available epidemiological evidence, by sex and age, that may help decision and policy makers form recommendations as to how much earlier colorectal cancer (CRC) screening should be initiated among people with a family history of CRC than among average-risk people. PATIENTS AND METHODS: Combining population-based cancer registry and health interview survey data from the United States and results of a recent meta-analysis of epidemiological studies, we estimated cumulative incidence of CRC within subsequent 10 yr (CI10) at various ages among men and women with and without a family history of CRC. We estimated both the CI10 levels reached in average-risk 45-, 50-, 55-, and 60-yr-old men and women and the age at which the same CI10 levels are reached in men and women with a history of CRC in a first-degree relative. RESULTS: Despite major differences in CRC risk by sex, and despite the strong age gradient in relative risk associated with a positive family history, “risk advancement periods” for those with a family history were consistently found to be between 9 and 11 yr for both sexes and at all four ages assessed. CONCLUSION: Advancement of first CRC screening by 10 yr among both men and women with a family history of CRC compared to the average-risk population ( e.g., from 50 to 40 yr of age) appears to be a reasonable, evidence-based recommendation. [ABSTRACT FROM AUTHOR]

In the statistical analysis of smoking cessation trials, participants with missing outcome data are commonly assumed to be continued smokers. Using algebraic formulas, a numerical example, and a real-life example, we evaluated the implications of nonresponse patterns on results obtained with a “missing = smoking” (MS) analysis compared with results obtained with an “available case” (AC) analysis, which excludes participants with missing outcome data. The algebraic formulas showed that MS and AC analysis provide consistent estimates of relative quit rates (RQR) when response rates in the treatment and control group are equal, regardless of the validity of the underlying assumption of both approaches. However, as shown in our numerical example, RQR estimated with both approaches can differ substantially in case of differential response rates. In the real-life example the proportion abstinent decreased from 16% to 5% in later response waves but did not reach zero. The estimates of the intervention effect from MS analysis and AC analysis converged when high and comparable response rates were achieved in both the treatment and control groups after multiple reminders. We conclude that smoking cessation studies should aim for high and equal response rates in the compared groups to ensure identification of all successful quitters and to be less susceptible to potential bias related to violation of the assumptions underlying the analytic strategies. [ABSTRACT FROM AUTHOR]

Objectives: To derive age and sex specific estimates of transition rates from advanced adenomas to colorectal cancer by combining data of a nationwide screening colonoscopy registry and national data on colorectal cancer (CRC) incidence. Design: Registry based study. Setting: National screening colonoscopy programme in Germany. Patients: Participants of screening colonoscopy in 2003 and 2004 (n = 840 149). Main outcome measures: Advanced adenoma prevalence, colorectal cancer incidence, annual and 10 year cumulative risk of developing CRC among carriers of advanced adenomas according to sex and age (range 55-80+ years) Results: The age gradient is much stronger for CRC incidence than for advanced adenoma prevalence. As a result, projected annual transition rates from advanced adenomas to CRC strongly increase with age (from 2.6% in age group 55-59 years to 5.6% in age group ⩾80 years among women, and from 2.6% in age group 55-59 years to 5.1% in age group ⩾80 years among men). Projections of 10 year cumulative risk increase from 25.4% at age 55 years to 42.9% at age 80 years in women, and from 25.2% at age 55 years to 39.7% at age 80 years in men. Conclusions: Advanced adenoma transition rates are similar in both sexes, but there is a strong age gradient for both sexes. Our estimates of transition rates in older age groups are in line with previous estimates derived from small case series in the pre-colonoscopy era independent of age. However, our projections for younger age groups are considerably lower. These findings may have important implications for the design of CRC screening programmes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Colonoscopy with removal of polyps may strongly reduce colorectal cancer (CRC) incidence and mortality. Recommended time intervals to surveillance colonoscopy differ between countries and have recently been extended to 5 yr or longer for the majority of cases in the United States. Whereas previous evidence is mainly based on observations of adenoma recurrence, we aimed to assess risk of CRC occurrence according to time since polypectomy. METHODS: In a population-based case-control study conducted in Germany, detailed history and results of previous large bowel endoscopies were obtained by interview and from medical records. Risk of CRC among subjects with history of endoscopic polypectomy compared to subjects without previous large bowel endoscopy was assessed according to time since polypectomy among 454 cases with CRC and 391 matched controls. RESULTS: Odds ratios (95% confidence intervals) of CRC up to 2 yr, 3–5 yr, and 6–10 yr after polypectomy (using subjects without previous endoscopy as reference group) were 0.16 (0.09–0.69), 0.27 (0.08–0.87), and 1.90 (0.67–5.43), respectively. Risk was significantly reduced (odds ratio 0.27, 95% confidence interval 0.10–0.77) within 5 yr even after detection and removal of high-risk polyps (3+ polyps, at least 1 polyp ≥1 cm, at least 1 polyp with villous components). Odds ratios (95% confidence intervals) for the entire 10-yr time interval following polypectomy were 0.50 (0.23–1.12) and 0.36 (0.18–0.76) for patients with recorded high-risk adenomas and other patients, respectively. CONCLUSIONS: Our study provides empirical support for extension of the surveillance interval after colonoscopic polypectomy to at least 5 yr. [ABSTRACT FROM AUTHOR]

Abstract: Helicobacter pylori infection is a strong risk factor for gastric cancer. A positive association with colorectal cancer has also been suggested, but available evidence remains inconclusive. In this population-based case-control study we investigated the association between H. pylori seroprevalence and colorectal adenocarcinoma under consideration of pro-inflammatory gene polymorphisms (384 incident cancer patients, 467 matched control subjects). Overall, the H. pylori seroprevalence was higher among cases (51%) than among controls (44%), and a positive association between H. pylori seroprevalence and colorectal adenocarcinoma risk was found, that persisted after adjustment for known potential confounders, including measures of socioeconomic status (odds ratio (OR)=1.41; 95% confidence intervals (CI), 1.06–1.87). Presence of specific H. pylori cytotoxin-associated gene A (CagA) antibodies did not significantly affect the observed risk. Additionally, a pro-inflammatory genotype did not increase the colorectal cancer risk associated with H. pylori infection. H. pylori positive subjects carrying the pro-inflammatory genotypes even had a lower risk. [Copyright &y& Elsevier]

Abstract: In many cancer registries, registration of new cases is somewhat less up-to-date than mortality follow-up. In such situations, hybrid analysis, a combination of cohort and period analysis, rather than ‘pure’ period analysis has been proposed to derive up-to-date survival estimates. We evaluate application and adaptation of a modelling strategy that has recently been introduced to enhance precision of period survival estimates, to ‘hybrid type of data’. Using data from the Finnish Cancer Registry, we show that modelling again strongly increases precision of survival estimates. Furthermore, special models adapted to the hybrid type of data are shown to provide even more precise and, in a clear majority of cases, also more valid predictions of survival of recently diagnosed patients than models ignoring the hybrid type of data. Finally, we show that model-based estimation of and testing for recent trends may give different answers if period rather than hybrid modelling is used for hybrid type of registry data. We conclude that modelling is useful for both hybrid and period analyses of cancer survival, but the different data structure needs to be taken into account in the set-up of models. [Copyright &y& Elsevier]

Objective: To evaluate new strategies to enhance the promotion of smoking cessation in general practice. Design: Cluster randomised trial, 2x2 factorial design. Setting: 82 medical practices in Germany, including 94 general practitioners. Participants: 577 patients who smoked at least 10 cigarettes per day (irrespective of their intention to stop smoking) and were aged 36-75 years. Interventions: Provision of a 2-h physician group training in smoking cessation methods and direct physician payments for every participant not smoking 12 months after recruitment (TI, training+incentive); provision of the same training and direct participant reimbursements for pharmacy costs associated with nicotine replacement therapy or bupropion treatment (TM, training+medication). Main outcome measure: Self-reported smoking abstinence obtained at 12 months follow-up and validated by serum cotinine. Results: In intention-to-treat analysis, smoking abstinence at 12 months follow-up was 3% (2/74), 3% (5/144), 12% (17/140) and 15% (32/219) in the usual care, and interventions TI, TM and TI+TM, respectively. Applying a mixed logistic regression model, no effect was identified for intervention TI (odds ratio (OR) 1.26, 95% confidence interval (CI) 0.65 to 2.43), but intervention TM strongly increased the odds of cessation (OR 4.77, 95% CI 2.03 to 11.22). Conclusion: Providing cost-free effective drugs to patients along with improved training opportunities for general practitioners could be an effective measure to achieve successful promotion of smoking cessation in general practice. [ABSTRACT FROM AUTHOR]