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Background: Subjective cognitive complaints (SCC) have been mostly studied in the context of Alzheimer's disease in memory clinic settings. The potential of combining SCC with genetic information and blood biomarkers of neurodegenerative diseases for risk assessment of dementia and depression in the absence of dementia among community-dwelling older adults has so far not been explored. Methods: Data were based on a population-based cohort of 6357 participants with a 17-year follow-up (ESTHER study) and a clinic-based cohort of 422 patients. Participants of both cohorts were grouped according to the diagnosis of dementia (yes/no) and the diagnosis of depression in the absence of dementia (yes/no). Participants without dementia included both cognitively unimpaired participants and cognitively impaired participants. Genetic information (APOE ε4 genotype) and blood-based biomarkers of neurodegenerative diseases (glial fibrillary acidic protein; GFAP, neurofilament light chain; NfL, phosphorylated tau181; p-tau181) were available in the ESTHER study and were determined with Simoa Technology in a nested case–control design. Logistic regression models adjusted for relevant confounders were run for the outcomes of all-cause dementia and depression in the absence of dementia. Results: The results showed that persistent SCC were associated both with increased risk of all-cause dementia and of depression without dementia, independently of the diagnostic setting. However, the results for the ESTHER study also showed that the combination of subjective complaints with APOE ε4 and with increased GFAP concentrations in the blood yielded a substantially increased risk of all-cause dementia (OR 5.35; 95%CI 3.25–8.81, p-value < 0.0001 and OR 7.52; 95%CI 2.79–20.29, p-value < 0.0001, respectively) but not of depression. Associations of NfL and p-tau181 with risk of all-cause dementia and depression were not statistically significant, either alone or in combination with SCC, but increased concentrations of p-tau181 seemed to be associated with an increased risk for depression. Conclusion: In community and clinical settings, SCC predict both dementia and depression in the absence of dementia. The addition of GFAP could differentiate between the risk of all-cause dementia and the risk of depression among individuals without dementia. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation is a central feature of several forms of dementia. However, few details on the associations of blood-based inflammation-related proteins with dementia incidence have been explored yet. Methods: The Olink Target 96 Inflammation panel was measured in baseline serum samples (collected 07/2000–06/2002) of 1782 older adults from a German, population-based cohort study in a case-cohort design. Logistic regression models were used to assess the associations of biomarkers with all-cause dementia, Alzheimer's disease, and vascular dementia incidence. Results: During 17 years of follow-up, 504 participants were diagnosed with dementia, including 163 Alzheimer's disease and 195 vascular dementia cases. After correction for multiple testing, 58 out of 72 tested (80.6%) biomarkers were statistically significantly associated with all-cause dementia, 22 with Alzheimer's disease, and 33 with vascular dementia incidence. We identified four biomarker clusters, among which the strongest representatives, CX3CL1, EN-RAGE, LAP TGF-beta-1, and VEGF-A, were significantly associated with dementia endpoints independently from other inflammation-related proteins. CX3CL1 (odds ratio [95% confidence interval] per 1 standard deviation increase: 1.41 [1.24–1.60]) and EN-RAGE (1.41 [1.25–1.60]) were associated with all-cause dementia incidence, EN-RAGE (1.51 [1.25–1.83]) and LAP TGF-beta-1 (1.46 [1.21–1.76]) with Alzheimer's disease incidence, and VEGF-A (1.43 [1.20–1.70]) with vascular dementia incidence. All named associations were stronger among APOE ε4-negative subjects. Conclusion: With this large, population-based cohort study, we show for the first time that the majority of inflammation-related proteins measured in blood samples are associated with total dementia incidence. Future studies should concentrate not only on single biomarkers but also on the complex relationships in biomarker clusters. [ABSTRACT FROM AUTHOR]

Background: Evidence-based guidance for starting ages of screening for first-degree relatives (FDRs) of patients with prostate cancer (PCa) to prevent stage III/IV or fatal PCa is lacking in current PCa screening guidelines. We aimed to provide evidence for risk-adapted starting age of screening for relatives of patients with PCa.Methods and Findings: In this register-based nationwide cohort study, all men (aged 0 to 96 years at baseline) residing in Sweden who were born after 1931 along with their fathers were included. During the follow-up (1958 to 2015) of 6,343,727 men, 88,999 were diagnosed with stage III/IV PCa or died of PCa. The outcomes were defined as the diagnosis of stage III/IV PCa or death due to PCa, stratified by age at diagnosis. Using 10-year cumulative risk curves, we calculated risk-adapted starting ages of screening for men with different constellations of family history of PCa. The 10-year cumulative risk of stage III/IV or fatal PCa in men at age 50 in the general population (a common recommended starting age of screening) was 0.2%. Men with ≥2 FDRs diagnosed with PCa reached this screening level at age 41 (95% confidence interval (CI): 39 to 44), i.e., 9 years earlier, when the youngest one was diagnosed before age 60; at age 43 (41 to 47), i.e., 7 years earlier, when ≥2 FDRs were diagnosed after age 59, which was similar to that of men with 1 FDR diagnosed before age 60 (41 to 45); and at age 45 (44 to 46), when 1 FDR was diagnosed at age 60 to 69 and 47 (46 to 47), when 1 FDR was diagnosed after age 69. We also calculated risk-adapted starting ages for other benchmark screening ages, such as 45, 55, and 60 years, and compared our findings with those in the guidelines. Study limitations include the lack of genetic data, information on lifestyle, and external validation.Conclusions: Our study provides practical information for risk-tailored starting ages of PCa screening based on nationwide cancer data with valid genealogical information. Our clinically relevant findings could be used for evidence-based personalized PCa screening guidance and supplement current PCa screening guidelines for relatives of patients with PCa. [ABSTRACT FROM AUTHOR]

Introduction: Determining potential risk factors of amyloid beta (Aβ) misfolding in blood, a risk marker for clinical Alzheimer’s disease (AD), could have important implications for its utility in future research and clinical settings. Methods: Participants aged 50 to 75 years attending a general health examination were recruited for a prospective community-based cohort study in Saarland, Germany, in 2000 to 2002. For these analyses, participants with available Aβ misfolding measurements and clinical AD information at 17-year follow-up were included (n = 444). Results: Age did not show any association with Aβ misfolding in plasma; however, a strong association of both age and Aβ misfolding with the incidence of clinical AD was evident. Education and cardiovascular diseases were likewise not associated with Aβ misfolding. Discussion: Structural measurement of Aβ misfolding in blood plasma is an age-independent risk marker of clinical AD among older adults, supporting that risk of clinical AD is already largely determined before older adulthood. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) incidence is increasing among young adults below screening age, despite the effectiveness of screening in older populations. Individuals with diabetes mellitus are at increased risk of early-onset CRC. We aimed to determine how many years earlier than the general population patients with diabetes with/without family history of CRC reach the threshold risk at which CRC screening is recommended to the general population.Methods and Findings: A nationwide cohort study (follow-up:1964-2015) involving all Swedish residents born after 1931 and their parents was carried out using record linkage of Swedish Population Register, Cancer Registry, National Patient Register, and Multi-Generation Register. Of 12,614,256 individuals who were followed between 1964 and 2015 (51% men; age range at baseline 0-107 years), 162,226 developed CRC, and 559,375 developed diabetes. Age-specific 10-year cumulative risk curves were used to draw conclusions about how many years earlier patients with diabetes reach the 10-year cumulative risks of CRC in 50-year-old men and women (most common age of first screening), which were 0.44% and 0.41%, respectively. Diabetic patients attained the screening level of CRC risk earlier than the general Swedish population. Men with diabetes reached 0.44% risk at age 45 (5 years earlier than the recommended age of screening). In women with diabetes, the risk advancement was 4 years. Risk was more pronounced for those with additional family history of CRC (12-21 years earlier depending on sex and benchmark starting age of screening). The study limitations include lack of detailed information on diabetes type, lifestyle factors, and colonoscopy data.Conclusions: Using high-quality registers, this study is, to our knowledge, the first one that provides novel evidence-based information for risk-adapted starting ages of CRC screening for patients with diabetes, who are at higher risk of early-onset CRC than the general population. [ABSTRACT FROM AUTHOR]

Background: The question of whether having a family history of prostatic borderline or in situ neoplasia (PBISN) is associated with an increased risk of invasive prostate cancer (PCa) or death from PCa remains unanswered. The objective of the current study was to provide an evidence-based risk estimation for the relatives of patients with PBISN.Methods: Nationwide Swedish family cancer data sets were used for the current study, including data regarding all residents of Sweden who were born after 1931 and their parents. Standardized incidence ratios (SIRs), standardized mortality ratios (SMRs), and lifetime cumulative risks of PCa were calculated for men with different constellations of family history. Family history was defined as a dynamic (time-dependent) variable considering changes during follow-up (1958-2015).Results: Of the 6,343,727 men in the current study, a total of 238,961 developed invasive PCa and 5756 were diagnosed with PBISN during the follow-up. Men with 1 first-degree relative who was diagnosed with PBISN had a 70% increased risk of invasive PCa (SIR, 1.7; 95% confidence interval, 1.5-1.9) and PCa death (SMR, 1.7; 95% confidence interval, 1.3-2.2) compared with men with no family history of PBISN or invasive PCa. These were rather close to estimates in men with 1 first-degree relative diagnosed with invasive PCa (SIR, 2.1 and SMR, 1.8). A higher risk of PCa in family members was found among patients with a family history of PBISN and/or PCa diagnosed before age 60 years. The results in terms of cumulative risk resembled this trend.Conclusions: A family history of PBISN appears to be as important as a family history of invasive PCa with regard to an increased risk of invasive PCa or PCa mortality. Such a history should not be overlooked in PCa screening recommendations or in future research regarding familial PCa. [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]

Oxidative stress contributes to endothelial dysfunction and is involved in the pathogenesis of myocardial infarction (MI) and stroke. However, associations of biomarkers of oxidative stress with MI and stroke have not yet been addressed in large cohort studies. A nested case–control design was applied in four population-based cohort studies from Germany, Czech Republic, Poland and Lithuania. Derivatives of reactive oxygen metabolites (d-ROMs) levels, as a proxy for the reactive oxygen species burden, and total thiol levels (TTL), as a proxy for the reductive capacity, were measured in baseline serum samples of 476 incident MI cases and 454 incident stroke cases as well as five controls per case individually matched by study center, age and sex. Statistical analyses were conducted with multi-variable adjusted conditional logistic regression models. d-ROMs levels were associated with both MI (odds ratio (OR), 1.21 [95% confidence interval (CI) 1.05–1.40] for 100 Carr units increase) and stroke (OR, 1.17 [95% CI 1.01–1.35] for 100 Carr units increase). TTL were only associated with stroke incidence (OR, 0.79 [95% CI 0.63-0.99] for quartiles 2–4 vs. quartile 1). The observed relationships were stronger with fatal than with non-fatal endpoints; association of TTL with fatal MI was statistically significant (OR, 0.69 [95% CI 0.51–0.93] for 100 μmol/L-increase). This pooled analysis of four large population-based cohorts suggests an important contribution of an imbalanced redox system to the etiology of mainly fatal MI and stroke events. [ABSTRACT FROM AUTHOR]

Objectives To investigate the relationship between polypharmacy and frailty. Design Longitudinal, observational cohort study. Setting Saarland, Germany. Participants 3,058 community-dwelling adults aged between 57 and 84 years. Measurements Frailty was assessed according to the frailty phenotype, described by Fried et al. Polypharmacy and hyperpolypharmacy were defined as the concomitant use of five or more and 10 or more drugs, respectively. We assessed associations between polypharmacy and prevalent and incident frailty within 3 years of follow-up by logistic regression models controlled for multiple potential confounders including comorbidity. Additionally, cubic splines were used to assess dose-response associations. Results Polypharmacy was reported in 39.1% (n = 1,194), and hyperpolypharmacy in 8.9% (n = 273) of participants. Prevalent frailty was present in 271 (8.9%) participants; 186 (9.3%) of 1,998 non-frail participants with follow-up data became frail within 3 years. After adjustment, polypharmacy and hyperpolypharmacy were associated with prevalent frailty with adjusted odds ratios (95% confidence interval) of 2.30 (1.60-3.31) and 4.97 (2.97-8.32), respectively. Polypharmacy (odds ratio ( OR) 1.51 (1.05-2.16)) and hyperpolypharmacy ( OR 1.90 (1.10-3.28)) were also independent predictors of incident frailty. Furthermore, there was a moderate exposure-response relationship between the number of medicines and prevalent as well as incident frailty. Conclusion Our study showed that polypharmacy is associated with frailty. Further research should address the potential benefit of reducing of inappropriate polypharmacy and better pharmacotherapeutic management for preventing medication-associated frailty. [ABSTRACT FROM AUTHOR]

Background: Disability-adjusted life-years (DALYs) are an indicator of mortality, morbidity, and disability. We calculated DALYs for cancer in middle-aged and older adults participating in the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) consortium.Methods: A total of 90 199 participants from five European cohorts with 10 455 incident cancers and 4399 deaths were included in this study. DALYs were calculated as the sum of the years of life lost because of premature mortality (YLLs) and the years lost because of disability (YLDs). Population-attributable fractions (PAFs) were also estimated for five cancer risk factors, ie, smoking, adiposity, physical inactivity, alcohol intake, and type II diabetes.Results: After a median follow-up of 12 years, the total number of DALYs lost from cancer was 34 474 (382 per 1000 individuals) with a similar distribution by sex. Lung cancer was responsible for the largest number of lost DALYs (22.9%), followed by colorectal (15.3%), prostate (10.2%), and breast cancer (8.7%). Mortality (81.6% of DALYs) predominated over disability. Ever cigarette smoking was the risk factor responsible for the greatest total cancer burden (24.0%, 95% confidence interval [CI] = 22.2% to 26.0%), followed by physical inactivity (4.9%, 95% CI = 0.8% to 8.1%) and adiposity (1.8%, 95% CI = 0.2% to 2.8%).Conclusions: DALYs lost from cancer were substantial in this large European sample of middle-aged and older adults. Even if the burden of disease because of cancer is predominantly caused by mortality, some cancers have sizeable consequences for disability. Smoking remained the predominant risk factor for total cancer burden. [ABSTRACT FROM AUTHOR]

Background: The concept of frailty is rapidly gaining attention as an independent syndrome with high prevalence in older adults. Thereby, frailty is often related to certain adverse outcomes like mortality or disability. Another adverse outcome discussed is increased health care utilization. However, only few studies examined the impact of frailty on health care utilization and corresponding costs. The aim of this study was therefore to investigate comprehensively the relationship between frailty, health care utilization and costs.Methods: Cross sectional data from 2598 older participants (57-84 years) recruited in the Saarland, Germany, between 2008 and 2010 was used. Participants passed geriatric assessments that included Fried's five frailty criteria: weakness, slowness, exhaustion, unintentional weight loss, and physical inactivity. Health care utilization was recorded in the sectors of inpatient treatment, outpatient treatment, pharmaceuticals, and nursing care.Results: Prevalence of frailty (≥3 symptoms) was 8.0%. Mean total 3-month costs of frail participants were €3659 (4 or 5 symptoms) and €1616 (3 symptoms) as compared to €642 of nonfrail participants (no symptom). Controlling for comorbidity and general socio-demographic characteristics in multiple regression models, the difference in total costs between frail and non-frail participants still amounted to €1917; p < .05 (4 or 5 symptoms) and €680; p < .05 (3 symptoms). Among the 5 symptoms of frailty, weight loss and exhaustion were significantly associated with total costs after controlling for comorbidity.Conclusions: The study provides evidence that frailty is associated with increased health care costs. The analyses furthermore indicate that frailty is an important factor for health care costs independent from pure age and comorbidity. Costs were rather attributable to frailty (and comorbidity) than to age. This stresses that the overlapping concepts of multimorbidity and frailty are both necessary to explain health care use and corresponding costs among older adults. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease is a leading cause of death in older people, and the impact of being exposed or not exposed to preventive cardiovascular medicines is accordingly high. Underutilization of beneficial drugs is common, but prevalence estimates differ across settings, knowledge on predictors is limited, and clinical consequences are rarely investigated. Methods: Using data from a prospective population-based cohort study, we assessed the prevalence, determinants, and outcomes of medication underuse based on cardiovascular criteria from Screening Tool To Alert to Right Treatment (START). Results: Medication underuse was present in 69.1% of 1454 included participants (mean age 71.1 ± 6.1 years) and was significantly associated with frailty (odds ratio: 2.11 [95% confidence interval: 1.24–3.63]), body mass index (1.03 [1.01–1.07] per kg/m2), and inversely with the number of prescribed drugs (0.84 [0.79–0.88] per drug). Using this information for adjustment in a follow-up evaluation (mean follow-up time 2.24 years) on cardiovascular and competing outcomes, we found no association of medication underuse with cardiovascular events (fatal and non-fatal) (hazard ratio: 1.00 [0.65–1.56]), but observed a significant association of medication underuse with competing deaths from non-cardiovascular causes (2.52 [1.01–6.30]). Conclusion: Medication underuse was associated with frailty and adverse non-cardiovascular clinical outcomes. This may suggest that cardiovascular drugs were withheld because of serious co-morbidity or that concurrent illness can preclude benefit from cardiovascular prevention. In the latter case, adapted prescribing criteria should be developed and evaluated in those patients. [ABSTRACT FROM AUTHOR]

Introduction Asthma is associated with diminished health-related quality of life ( HRQoL). Particularly in adolescence, asthma may be under-diagnosed and undertreated or poorly managed. Therefore, we aimed to determine the association between childhood wheezing phenotypes rather than asthma and adolescent HRQoL in children aged 10-17 yr. Methods We analyzed the data from two prospective population-based cohort studies (n = 604 and n = 1804) conducted in southern Germany with baseline assessments in 2000 and 2006 and follow-ups at frequent intervals. Parent-reported wheeze was categorized into never, early transient, persistent, and late-onset wheeze. We assessed child-reported HRQoL in seven scales using the validated KINDL-R. Multivariate linear regression models were computed. Results Participants with late-onset wheeze had significantly lower values in all HRQoL scales, but physical well-being compared to never wheezers. Early transient wheeze was negatively associated with three HRQoL scales only (family, school, and total). These effects were confined to the oldest age group (≥13.5 yr) in one study. Persistent wheeze was not associated with HRQoL. Conclusions In teenagers, late-onset wheezers seem to be particularly vulnerable for impairments in psychosocial aspects of health-related quality of life. They may therefore require particular attention with regard to education about asthma management and potentially family-based psychosocial intervention. [ABSTRACT FROM AUTHOR]

Obesity has been linked with elevated levels of C-reactive protein (CRP), and both have been associated with increased risk of mortality and cardiovascular disease (CVD). Previous studies have used a single 'baseline' measurement and such analyses cannot account for possible changes in these which may lead to a biased estimation of risk. Using four cohorts from CHANCES which had repeated measures in participants 50 years and older, multivariate time-dependent Cox proportional hazards was used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) to examine the relationship between body mass index (BMI) and CRP with all-cause mortality and CVD. Being overweight (≥25-<30 kg/m) or moderately obese (≥30-<35) tended to be associated with a lower risk of mortality compared to normal (≥18.5-<25): ESTHER, HR (95 % CI) 0.69 (0.58-0.82) and 0.78 (0.63-0.97); Rotterdam, 0.86 (0.79-0.94) and 0.80 (0.72-0.89). A similar relationship was found, but only for overweight in Glostrup, HR (95 % CI) 0.88 (0.76-1.02); and moderately obese in Tromsø, HR (95 % CI) 0.79 (0.62-1.01). Associations were not evident between repeated measures of BMI and CVD. Conversely, increasing CRP concentrations, measured on more than one occasion, were associated with an increasing risk of mortality and CVD. Being overweight or moderately obese is associated with a lower risk of mortality, while CRP, independent of BMI, is positively associated with mortality and CVD risk. If inflammation links CRP and BMI, they may participate in distinct/independent pathways. Accounting for independent changes in risk factors over time may be crucial for unveiling their effects on mortality and disease morbidity. [ABSTRACT FROM AUTHOR]

Lower respiratory tract infections (LRTIs) are a major cause of hospitalization in infants. Research suggests that immunomodulatory properties of vitamin D may influence LRTI risk. This study's objective was to examine whether 25-hydroxyvitamin D [25(OH)D] concentrations in cord blood influenced susceptibility to LRTI in the first year of life. Data was analyzed from a prospective birth cohort of 777 mother-infant pairs based in Ulm, Germany. Relative risks (RRs) of LRTI in relation to 25(OH)D cord blood levels were estimated by log-binomial regression after adjustment for potential confounders. To account for seasonal variation in both vitamin D levels and infections, we examined the association in different seasons. Analyses were conducted using clinical predefined cutpoints, quartiles, and season-standardized 25(OH)D quartiles. We observed a statistically significant association between 25(OH)D status in cord blood and risk of LRTI across the year using clinical cutpoints. The adjusted RR of LRTI for individuals with vitamin D deficiency (<25 nmol/L) in comparison to the referent category (>50 nmol/L) was 1.32 [95 % confidence interval (CI) 1.00, 1.73]. The association differed by maternal allergy status; children born to mothers without allergy demonstrated a RR of 1.45 (95 % CI 1.03, 2.03). The effect was largely driven by a strong association between 25(OH)D and LRTI in infants born in fall with a RR of 3.07 (95 % CI 1.37, 6.87). Our findings suggest that vitamin D deficiency at birth is associated with increased risk of LRTI particularly in infants born to mothers without allergy. The association seems strongest in infants born in fall. [ABSTRACT FROM AUTHOR]

Although a positive association between type 2 diabetes mellitus (T2DM) and colorectal cancer is well established, uncertainty exists about risk differences in diabetic men and women when considering colorectal neoplasia (CN). The main objective was to examine gender-specific associations of T2DM with CN in a population-based cohort study of adults in Germany. This analysis is based on participants of the ESTHER-study, a population-based cohort study. Participants were 50-74 years old at baseline and underwent colonoscopy during 5 year follow-up. CN detected at colonoscopy were validated by medical records review. Total and gender-specific associations of T2DM at baseline and CN were estimated using log-binomial regression. Overall, 55 cases of CN were detected in 166 participants with T2DM and 328 cases in 1,360 participants without T2DM. In women, CN was found in 32 % of participants with T2DM and in 18 % without T2DM (adjusted prevalence ratio (PR): 1.66 95 % CI 1.04-2.64). In men, prevalence for CN was 35 % for those with T2DM and 33 % for those without T2DM (adjusted PR = 1.01; 95 % CI 0.71-1.43). T2DM might have a stronger impact on CN among women than among men. Further research should examine possible reasons for these differences. [ABSTRACT FROM AUTHOR]

The aim of this analysis is to compare screening strategies with haemoglobin A (HbA), fasting plasma glucose (FPG) or combined measures in the identification of individuals at high risk for diabetes. Applying American Diabetes Association thresholds for FPG and HbA screening, 6,803 subjects free of diabetes were classified as non-diabetic, pre-diabetic and possibly diabetic by FPG (<100, 100-125 and >125 mg/dl) and HbA (<5.7, 5.7-6.4 and >6.4%). Hazard ratios, sensitivity and specificity were estimated for individuals with pre-diabetes with respect to incident diabetes in the following 5 years. Areas under the receiver operating characteristic curves (AUC) were estimated for levels of FPG ≤ 125 mg/dl and HbA ≤ 6.4% in diabetes prediction. Although FPG and HbA screenings poorly agreed in classifying individuals as pre-diabetic, hazard ratios [95% confidence interval] for incident diabetes were similarly increased in univariate models in the two pre-diabetic groups: FPG 100-125 mg/dl, 4.72 [3.69; 6.05]; HbA 5.7-6.4%, 3.97 [3.05; 5.23]. HbA and FPG had comparable AUCs (FPG, 0.732; HbA, 0.725) and consequently similar 5-year sensitivities and specificities for their pre-diabetes definitions (when the lower cut-off for HbA-defined pre-diabetes was increased to a level between 5.8 and 5.9%). Combining HbA and FPG increased the AUC to 0.778, and a further increase to 0.817 was seen with additional inclusion of conventional risk factors. FPG and HbA have comparable (yet insufficient) abilities in identifying individuals at high risk for diabetes. Effectiveness of a diabetes screening program could be improved by a risk score including FPG and HbA. [ABSTRACT FROM AUTHOR]

Background and objective Recent longitudinal studies have suggested an association of high serum parathyroid hormone levels (PTH) with elevated cardiovascular risk in the general population. This study presents analyses of the prognostic value of baseline PTH for subsequent cardiovascular events and all-cause mortality in a highrisk population with stable coronary heart disease. Methods Based on measurements of PTH levels in 1133 patients recruited at two German rehabilitation clinics and followed over 8 years, multivariate Cox regression analysis was performed to estimate the risk of secondary cardiovascular events (including myocardial infarction, stroke and death due to cardiovascular diseases) and allcause- mortality according to PTH quartiles (Q1eQ4) and continuous PTH concentrations. Results During follow-up, 153 cardiovascular events and 124 deaths occurred. Age and sex-adjusted Cox regression analysis yielded statistically significant positive associations of PTH with both cardiovascular event incidence and all-cause mortality (HR (95% CI) per SD increase of PTH: 1.35 (1.21e1.51) and 1.25 (1.11e1.42), respectively). Associations remained essentially unchanged after additional adjustment for multiple cardiovascular risk factors. More detailed doseeresponse analyses showed strong risk elevation for above-normal levels of PTH (>95th percentile), with essentially no association at lower levels. Conclusion The results of this first detailed study in a cohort of patients with stable coronary heart disease suggest an independent predictive value of above-normal PTH for the prognosis in patients with stable coronary heart disease. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2010; 40 (7): 616–622 Background The impact of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is a matter for ongoing debate. In this study, we analyse associations of CETP with cardiovascular endpoints in a cohort of patients with stable coronary artery disease (CAD). Design KAROLA is a prospective observational study of patients with CAD and a median follow-up of 8 years ( n = 1132). CETP levels were measured using an enzyme-linked immunosorbent assay. Results Cholesteryl ester transfer protein levels were lower in men ( P = 0·0016), positively correlated to low-density lipoprotein cholesterol, and inversely correlated to triglyceride levels ( P < 0·0001 and P = 0·011 respectively). There was no significant difference in mortality between patients in different CETP quartiles; the hazard ratio of lowest vs. highest quartile was 1·33 (95% confidence interval (CI): 0·77–2·30) for mortality and 1·24 (95% CI: 0·75–2·03) for secondary events. In post hoc analyses, comparing nondiabetic subjects with CETP below vs. above median, the adjusted hazard ratio for death in patients with low CETP levels was 1·84 (95% CI: 1·10–3·09). Conclusion Although statistically significant associations were found only in post hoc analyses, the effect sizes in this study were in line with previous findings in the Framingham and LURIC population. In combination, the emerging evidence challenges the concept of pharmacological CETP inhibition. [ABSTRACT FROM AUTHOR]

Available long-term survival figures for patients with Hodgkin's lymphoma (HL) from population-based cancer registries mostly refer to patients diagnosed in the 1980s and 1990s, and do not reflect recent progress in and spread of effective therapy at the population level. Using data from the Surveillance, Epidemiology, and End Results program, we employed a novel model-based projection method to estimate 5- and 10-year relative survival expectations of HL patients in the U.S. diagnosed in 2006-2010. Preliminary empirical evaluation of the method using historical data indicates excellent performance. Projections of 10-year relative survival percentages and their standard errors by age groups are as follows: 15-24 y: 94.7 (1.1), 25-34 years, 89.4 (1.5); 35-44 years, 90.1 (1.6); 45-54 years, 83.6 (2.7); 55-64 years, 70.5 (4.7); 65-74 years, 48.5 (5.9); and 75+ years, 24.0 (5.7). These estimates are 2.5-11.1 percentage points higher than those obtained by standard cohort analysis from the same database (pertaining to patients diagnosed in 1991-1995). Patients diagnosed with HL in 2006-2010 have higher long-term survival expectations than suggested by conventional survival statistics from population-based cancer registries. The 10-year survival expectations are now close to or exceed 90% in all age groups up to age 45, and exceed 80% and 70% in the 45-54 and 55-64 age groups, respectively. [ABSTRACT FROM AUTHOR]

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]

Purpose: Early detection of prostate cancer by prostate specific antigen testing is subject to ongoing controversy. Thus, practical tests to improve or replace prostate specific antigen would be highly desirable. In diagnostic studies promising results were shown for myeloid related protein-14 in serum and urine. However, confirmation in longitudinal population based studies is needed. Materials and Methods: Incident prostate cancer cases (32) and controls (74) matched by age were identified during a 2-year followup of a longitudinal study. The group of cases was further complemented by a sample of 24 prostate cancer cases recruited before initiation of treatment from a clinical study. A commercially available test was used to analyze serum and urinary myeloid related protein-14 in blinded fashion. Results: In contrast to prostate specific antigen, serum and urinary myeloid related protein-14 could not significantly discriminate between prostate cancer cases and controls. Conclusions: In our study neither serum nor urinary myeloid related protein-14 proved suitable to distinguish prostate cancer cases from controls. Overall myeloid related protein-14 performed much worse than prostate specific antigen and it does not seem useful to reduce false-positive findings of prostate specific antigen in the controversial range of 4 to 10 ng/ml. [Copyright &y& Elsevier]

Background: To describe hospitalisations of nursing home (NH) residents in Germany during their last months of life. Methods: Retrospective cohort study on 792 NH residents in the Rhine-Neckar region in South- West Germany, newly institutionalized in the year 2000, who died until the study end (December 2001). Baseline variables were derived from a standardized medical examination routinely conducted by the medical service of the health care insurance plans in Germany. Information on hospitalisations and deaths was extracted form records of the pertinent health insurance plans. Results: NH residents who died after NH stay of more than 1 year spent 5.8% of their last year of life in hospitals. Relative time spent in hospitals increased from 5.2% twelve months before death (N = 139 persons) to 24.1% in their last week of life (N = 769 persons). No major differences could be observed concerning age, gender or duration of stay in NH. Overall, 229 persons (28.9%) died in hospital. Among these, the last hospital stay lasted less than 3 days for 76 persons (31.9%). Another 25 persons (3.2%) died within three days after hospital discharge. Conclusion: Our study indicates that proximity of death is the most important driver of health care utilization among NH residents. The relation of age or gender to health care expenditures seem to be weak once time to death is controlled for. Duration of NH stay does not markedly change rates of hospitalisation during the last months of life. [ABSTRACT FROM AUTHOR]

Background: Wide implementation of mammography screening has resulted in increased numbers of women diagnosed with breast carcinoma in situ. We aimed to determine the risk of invasive breast cancer in relatives of patients with breast carcinoma in situ in comparison to the risk in relatives of patients with invasive breast cancer.Methods: We analyzed the occurrence of cancer in a nationwide cohort including all 5,099,172 Swedish women born after 1931 with at least one known first-degree relative. This was a record linkage study of Swedish family cancer datasets, including cancer registry data collected from January 1, 1958, to December 31, 2015. We calculated standardized incidence ratios (SIRs) and 10-year cumulative risk of breast cancer diagnosis for women with a family history of in situ and invasive breast cancer.Results: Having one first-degree relative with breast carcinoma in situ was associated with 50% increased risk of invasive breast cancer (SIR = 1.5, 95% CI 1.4-1.7) when compared to those who had no family history of invasive breast cancer or breast carcinoma in situ in either first- or second-degree relatives. Similarly, having one first-degree relative with invasive breast cancer was associated with 70% (1.7, 1.7-1.8) increased risk. The 10-year cumulative risk for women at age 50 with a relative with breast carcinoma in situ was 3.5% (2.9-3.9%) and was not significantly different from 3.7% (3.6-3.8%) risk for 50-year-old women with a relative with invasive breast cancer (95% confidence intervals overlapped).Conclusions: The risk of invasive breast cancer for women with a family history of breast carcinoma in situ was comparable to that for women with a family history of invasive breast cancer. Therefore, family history of breast carcinoma in situ should not be overlooked in recommendations for breast cancer prevention for women with a family history of breast cancer. [ABSTRACT FROM AUTHOR]

Background & aims: Infection with Helicobacter pylori (H pylori) is a risk factor for peptic ulcer disease (PUD), but there are limited longitudinal data on the associations between infection and incident gastric or duodenal ulcers. Methods: Information on potential risk factors, lifetime history of PUD, and serologic measurements of H pylori infection were obtained from a German cohort of 9953 adults, 50 to 74 years old at baseline (2000–2002). The incidence of ulcers was determined by questionnaires sent to study participants and general practitioners 2 and 5 years later, and was validated by medical records. Results: A lifetime history of PUD was reported by 1030 participants, and during the follow-up period 48 had a first gastric and 22 had a first duodenal ulcer. Infection with H pylori strains that express cytotoxin-associated gene A (cagA) was significantly associated with a lifetime history of PUD (odds ratio, 1.75; 95% confidence interval [CI], 1.50–2.04). Based on longitudinal analyses with physician-validated end points, the adjusted hazard ratios for incident gastric and duodenal ulcer disease were 2.9 (95% CI, 1.5–5.5) and 18.4 (95% CI, 4.2–79.9), respectively, among patients infected with cagA-positive strains of H pylori. Conclusions: In cross-sectional analysis, infection with cagA-positive strains of H pylori was associated with a 1.75-fold increased risk of peptic ulcer disease. Longitudinal analyses revealed an 18.4- and 2.9-fold increased risk for duodenal ulcer and gastric ulcer, respectively. The proportion of PUD that is attributable to H pylori infection might be larger than previously believed. [Copyright &y& Elsevier]

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). DISCUSSION: In this large prospective cohort study from Germany, screening colonoscopy was associated with strong reduction in CRC incidence and mortality. [ABSTRACT FROM AUTHOR]

Both telomere length and frailty were observed to be associated with aging. Whether and to what extent telomere length is related to frailty is essentially unknown. In this cross-sectional analysis of baseline data of 3537 community-dwelling adults aged 50 to 75 years of a large German cohort study, we assessed the hypothesis that shorter telomere length might be a biological marker for frailty. Using whole blood DNA we examined mean telomere repeat copy to single gene copy number (T/S ratio) using quantitative PCR. Construction of a frailty index (FI) was based on a deficit accumulation approach, which quantifies frailty as ratio of the deficits present divided by the total number of deficits considered. Mean FI was determined according to age by tertiles of T/S ratio. Furthermore, we used correlation analyses stratified for gender and age groups to examine the association of the T/S ratio with frailty. Mean FI value was similar across tertiles of the T/S ratio (0.24 ± 0.14, 0.24 ± 0.14 and 0.23 ± 0.14, respectively (p = 0.09)), and FI and the T/S ratio were uncorrelated in gender- and age-specific analyses. In conclusion, T/S ratio and frailty were unrelated in this large sample of older adults. T/S ratio may therefore not be a meaningful biological marker for frailty. [ABSTRACT FROM AUTHOR]

Cross-sectional studies have consistently shown an association between current smoking and oxidative stress biomarkers. However, no longitudinal studies have been performed so far. The oxidative stress biomarkers "total thiol groups of serum proteins" (TTP), and "derivatives of reactive oxygen metabolites" (D-ROM) were measured in serum samples of 3835 participants of a population-based, German cohort study of older adults (age: 60–84 years) with repeated measurements for 2834 participants three years later. Multivariable linear regression models were applied and β-coefficients with 95% confidence intervals were obtained. In both cross-sectional and longitudinal analysis, current smoking was statistically significantly associated with increased D-ROM levels, and a dose-response relationship between the amount of daily tobacco consumption and the D-ROM concentrations was observed that plateaued at ≥15 g of tobacco consumption per day. Former smoking was also associated with D-ROM levels. Only former smokers who quitted smoking more than 10 years ago had no increased D-ROM levels compared to never smokers. There was neither a cross-sectional nor longitudinal association between any of the smoking variables and TTP levels. This large population-based cohort of older German adults suggests that smoking has long-term effects on the oxidative stress burden. The further increasing D-ROM levels of current smokers at an older age and the observation that it may take more than 10 years until the redox balance is restored are solid arguments for quitting smoking as soon as possible at any age. • First longitudinal analysis on current smoking and oxidative stress biomarkers. • Biomarkers TTP and D-ROM measured in n = 2834 older German adults three years apart. • D-ROM but not TTP levels were longitudinally associated with current smoking. • Smoking cessation >10 years ago needed for D-ROM levels similar to never smokers. • Smoking may have long-term effects on the oxidative stress burden. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To provide a systematic review and meta-analysis of prospective, population-based cohort studies on the association of serum 25-hydroxyvitamin D (25(OH)D) and all-cause mortality. Methods: Relevant studies were identified by systematically searching Medline, EMBASE and ISI Web of Knowledge. Reported hazard ratios (HRs) for 25(OH)D categories were recalculated employing comprehensive trend estimation from summarized dose-response data and pooled in a random effects model meta-analysis. Results: Overall, 12 original studies were included in the review and meta-analysis comprising 32,142 mainly elderly study participants with measured 25(OH)D of whom 6921 died during follow-up. An inverse association between 25(OH)D levels and all-cause mortality was found in all but two studies that was statistically significant in several of the individual studies. In meta-analysis, 25(OH)D levels were significantly inversely associated with all-cause mortality with a pooled HR of 0.92 (95% confidence interval: 0.89–0.95) for a 20nmol/l increase in 25(OH)D levels. Conclusion: In this meta-analysis of prospective, population-based cohort studies, a 20nmol/l increase in 25(OH)D levels was associated with an 8% lower mortality in the general elderly population. This agrees with results from meta-analyses on randomized controlled trials that found a decrease in mortality with vitamin D3 supplementation of a comparable magnitude. [Copyright &y& Elsevier]

Abstract: Background: New therapeutic options have led to substantial increases in survival expectations of patients with non-Hodgkin lymphoma (NHL) in recent years. In contrast to many malignancies, survival in older patients has improved in NHL at a rate similar to that in younger patients. In the past, the impact of innovations on long-term survival of NHL patients on the population level has been disclosed only with substantial delay. Methods: We employ a novel model-based projection method to estimate survival expectations of NHL patients age 60+ diagnosed in 2008–2012. Preliminary empirical evaluation of the method using historical data indicates excellent performance in projection of age specific and overall 5- and 10-year relative survival. Results: Overall 5- and 10-year survival projections for 2008–2012 were 67.5% and 56.9%, respectively, 8.2 percentage units (% units) and 15.2% units, respectively, higher than the most recent survival estimates available from traditional cohort analysis. Projected survival decreased with age, ranging from 79.1% for patients age 60–64 to 54.3% for patients age 80+. Projected survival estimates for diffuse large B-cell lymphoma and follicular lymphoma were 59% and 84.9%, respectively. Survival estimates by model-based projection were substantially higher than available cohort estimates for all age groups including 80+, each specific morphology examined, nodal and extranodal disease, and both genders. Conclusions: Patients over 60 diagnosed with NHL in 2008–2012 have much higher long-term survival expectations than suggested by previously available survival statistics. [Copyright &y& Elsevier]

Abstract: Aims: Our main aim was to analyse gender differences in the association of adherence and poor glycaemic control (PGC) in a cohort of patients with type 2 diabetes mellitus in Germany. Methods: Baseline data of the DIANA-study, a prospective cohort study of type 2 diabetes mellitus patients in South-West Germany, were analysed. Information on medication adherence and factors related to PGC was obtained by self-administered questionnaire. PGC was defined as HbA1c ≥7.5%. Bivariate and multivariate analyses using log-binomial regression were employed to assess overall and gender-specific associations of non-adherence and PGC. Results: 624 men and 518 women were included in the analyses. In total, 147 men (24%) and 114 women (23%) reported non-adherence to medication. In men, PGC was found in 37% of the participants reporting non-adherence and in 19% reporting adherence (adjusted prevalence ratio (PR)=1.90, 95%-CI: 1.46–2.49). In women, PGC was found in 19% of the participants reporting non-adherence and in 18% reporting adherence (adjusted PR=0.97, 95%-CI: 0.65–1.46). Conclusions: Our results show gender-specific differences in the association of adherence and PGC. This underlines the need for efforts to improve glycaemic control in patients with type 2 diabetes mellitus with a particular focus on men. [Copyright &y& Elsevier]

Abstract: Objective: There is debate whether infection with Helicobacter (H.) pylori, the main inducer of chronic atrophic gastritis (CAG), is a risk factor for cardiovascular disease and premature mortality. Methods: Serological measurements of H. pylori infection and pepsinogen (PG) I and II were obtained in a population-based German cohort of 9953 older adults (50–74 years). Cox regression was employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for myocardial infarction, stroke, cardiovascular and all-cause mortality during five-year follow-up. Results: According to serology, 4977 participants (51.9%) were infected with H. pylori (2604 with cytotoxin-associated gene A (cagA) strains) and 541 (5.7%) had CAG (PGI<70ng/mL and PGI/PGII<3). During follow-up, 540 participants died (163 from cardiovascular causes), 170 experienced a primary myocardial infarction and 241 had a stroke. Neither cytotoxin-associated gene A (cagA) negative nor cagA positive H. pylori infections were associated with an increased risk for myocardial infarction, stroke or all-cause mortality. Intriguingly, infection with cagA positive H. pylori strains was inversely associated with cardiovascular mortality (HR, 0.62; CI: 0.41–0.94). No statistically significant associations were observed for the small group of participants with CAG, but point estimates of adjusted HRs for myocardial infarction, stroke and cardiovascular mortality were all below 1 (0.71, 0.59 and 0.65, respectively). Conclusions: Our results do not support the hypothesis that H. pylori infection or CAG are risk factors for cardiovascular disease or mortality and instead suggest an inverse relationship of cagA positive H. pylori infection with fatal cardiovascular events. [Copyright &y& Elsevier]

Background & Aims: Associations of serum gamma-glutamyltransferase levels with a variety of incident diseases and mortality have been suggested. The present study attempted to expand the body of evidence to especially relevant occupational cohorts in which exposure to established γ-GT determinants may greatly differ from the general population. Methods: The study was based on occupational health examinations conducted from 1986 to 1992 in 19,090 German male workers from the construction industry, aged 25–64years. Sociodemographics and other health-related information were collected during the exam. Vital status follow-up was conducted through 2008. Associations of baseline γ-GT levels (measurements at 25°C) with all-cause and cause-specific mortality were examined by Kaplan–Meier plotting and multiple adjusted Cox regression models. Results: A total of 2170 deaths occurred during 303,198 person-years of follow-up. The risk of death due to any cause was 2.5-fold increased in subjects in the highest (⩾39U/L) versus lowest (<11U/L) γ-GT quintile. To varying extents, elevated γ-GT was associated with higher mortality due to cancer, circulatory, respiratory, and digestive causes, as well as accidents/poisoning. Conclusions: The findings in this cohort provide evidence for γ-GT being associated with a broad range of causes of death, including less investigated outcomes. Some characteristics of the observed patterns need to be seen in the context of our cohort, featuring particularly high γ-GT levels. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To review and summarize evidence from longitudinal studies on the association between serum 25-hydroxyvitamin D (25(OH)D) and the risk of prostate cancer (PC). Methods: Relevant prospective cohort studies and nested case-control studies published until July 2009 were identified by systematically searching Ovid Medline, EMBASE, and ISI Web of Knowledge databases and by cross-referencing. The following data were extracted in a standardized manner from eligible studies: first author, publication year, country, study design, characteristics of the study population, duration of follow-up, PC incidence/PC mortality according to serum vitamin D status and the respective risk ratios, and covariates adjusted for in the analysis. Due to the heterogeneity of studies in categorizing serum vitamin D levels, all results were recalculated for an increase in serum 25(OH)D by 10ng/ml. Summary odds ratios (ORs) were calculated using meta-analysis methods. Results: Overall, eleven original articles were included, ten of which reported on the association between serum vitamin D levels and PC incidence and one article reported on the association with PC mortality. Meta-analysis of studies on PC incidence resulted in a summary OR (95% confidence interval, CI) of 1.03 (0.96–1.11) associated with an increase of 25(OH)D by 10ng/ml (P =0.362). No indication for heterogeneity and publication bias was found. Conclusions: According to available evidence from longitudinal studies, serum 25(OH)D is not associated with PC incidence. [Copyright &y& Elsevier]

Background: Evidence has recently accumulated that single nucleotide polymorphisms in the genetic region encoding the nicotinic acetylcholine receptor subunits α-5, α-3, and β-4 are associated with smoking and nicotine dependence. We aimed to determine whether these genetic variations are also predictive of smoking cessation. Methods: Lifetime history of smoking was assessed by questionnaire at enrolment into a large epidemiological study of the German elderly population (ESTHER study). Cox proportional hazards modeling was applied in a retrospective cohort approach to determine the associations of individual polymorphisms and haplotypes with smoking cessation probability in 1446 subjects who reported regularly smoking more than 20 cigarettes at some point in their lives. Results: Given the genotype distributions and number of cessation events observed, the power to detect associations ranged from 54% to 97% for hazard ratios of 1.2 to 1.4 in case of the variant with strongest prior evidence (α = .05). Nonetheless, neither individual polymorphisms nor inferred multilocus haplotypes were significantly associated with smoking cessation. Conclusions: Although the robust association of the nicotinic acetylcholine receptor subunit genes investigated with smoking-related phenotypes is an apparent success story of genetic epidemiology, the respective variations seem to exert no relevant influence on smoking cessation probability in heavy smokers in the general population. [Copyright &y& Elsevier]

Abstract: The present study is aimed to compare survival and prognostic changes over time between elderly (70–84 years) and middle-aged cancer patients (55–69 years). We considered seven cancer sites (stomach, colon, breast, cervix and corpus uteri, ovary and prostate) and all cancers combined (but excluding prostate and non-melanoma skin cancers). Five-year relative survival was estimated for cohorts of patients diagnosed in 1988–1999 in a pool of 51 European populations covered by cancer registries. Furthermore, we applied the period-analysis method to more recent incidence data from 32 cancer registries to provide 1- and 5-year relative survival estimates for the period of follow-up 2000–2002. A significant survival improvement was observed from 1988 to 1999 for all cancers combined and for every cancer site, except cervical cancer. However, survival increased at a slower rate in the elderly, so that the gap between younger and older patients widened, particularly for prostate cancer in men and for all considered cancers except cervical cancer in women. For breast and prostate cancers, the increasing gap was likely attributable to a larger use of, respectively, mammographic screening and PSA test in middle-aged with respect to the elderly. In the period analysis of the most recent data, relative survival was much higher in middle-aged patients than in the elderly. The differences were higher for breast and gynaecological cancers, and for prostate cancer. Most of this age gap was due to a very large difference in survival after the 1st year following the diagnosis. Differences were much smaller for conditional 5-year relative survival among patients who had already survived the first year. The increase of survival in elderly men is encouraging but the lesser improvement in women and, in particular, the widening gap for breast cancer suggest that many barriers still delay access to care and that enhanced prevention and clinical management remain major issues. [Copyright &y& Elsevier]