Stage of cancer diagnoses among migrants from the former Soviet Union in comparison to the German population – are diagnoses among migrants delayed?

Background: In this study, we compared stage at diagnosis, standardized incidence ratio (SIR) and standardized mortality ratio (SMR) of most frequent cancer diagnoses between re-settlers (Aussiedler) from the former Soviet Union and the general population in the Saarland in Germany to assess possible delays in diagnosis of cancer among this migrant group. Methods: Lung cancer, colorectal cancer, breast cancer, prostate cancer, malignant melanoma of the skin and stomach cancer diagnoses among a cohort of 18,619 re-settlers living in the Saarland between 1990 and 2009 were identified by the federal state’s cancer registry. Vital status was available for the respective time-period and used to calculate SIR and SMR in comparison to the autochthonous population. Tumor stages were condensed into local and advanced stages. Odds ratios (OR) for an advanced tumor stage were modeled in dependence of re-settler-status and relevant covariates by logistic regression. Missing values were addressed in a sensitivity analysis. The influence of duration of stay in Germany on advanced stage diagnosis was analyzed among re-settlers. Results: SIR and SMR of lung and breast cancer were lower among female re-settlers, while SIR and SMR of colorectal and prostate cancer were lower among male re-settlers. SIR and SMR of stomach cancer were elevated among both sexes. Female re-settlers showed an elevated OR for being diagnosed with advanced stage breast cancer. Both male and female re-settlers showed an elevated OR when observing all six sites combined (OR among males 1.47, p = 0.04; OR among females 1.37, p = 0.05). The result of elevated ORs was supported in the sensitivity analysis. Finally, male re-settlers showed a weak association between duration of stay in Germany and reduced risk for advanced stage diagnosis. Conclusion: Re-settlers were more likely to be diagnosed at an advanced tumor stage. These findings are in line with previous research having shown unfavorable health care utilization of re-settlers. Overall, low mortality rates despite an increased risk of advanced stage at diagnosis argue for a sufficient follow-up care, comparable to the autochthonous population

Risk of contralateral second primary breast cancer according to hormone receptor status in Germany

Introduction: Hormone receptor (HR) status has become an established target in treatment strategies of breast cancer. Population-based estimates of contralateral breast cancer (CBC) incidence by HR subtype in particular are limited. The aim of this study was to provide detailed data on CBC incidence for Germany. Methods: Invasive breast cancer data were extracted on 49,804 women yielding 594 second primaries from the cancer registries of the Federal States of Brandenburg and Saarland and the area of Munich for the period from 1998 to 2007. Multiple imputation was used on missing values for HR status. We estimated standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs). Results: SIR estimates of CBC among women diagnosed with an invasive first primary breast cancer (FBC) of any HR subtype ranged from 1.0 to 1.5 in the three registries. Pooling three registries' data, the SIR of HR-positive CBC was 0.7 (95% CI: 0.6 to 0.8) among women with HR-positive FBC. For those women with HR-negative FBC, the SIR of HR-negative CBC was 8.9 (95% CI: 7.1 to 11.1). Among women with FBC diagnosed before the age of 50 years, incidence of CBC was increased, especially for HR-negative FBC (SIR: 9.2; 95% CI: 7.1 to 11.9). Conclusions: HR status of the first primary and age at first diagnosis is relevant for predicting risk of CBC. Particularly, patients with HR-negative FBC had elevated risks

Analysing horizontal equity in enrolment in Disease Management Programmes for coronary heart disease in Germany 2008–2010

Background: Disease Management Programmes (DMPs) have been introduced in Germany ten years ago with the aim to improve effectiveness and equity of care, but little is known about the degree to which enrolment in the programme meets the principles of equity in health care. We aimed to analyse horizontal equity in DMP enrolment among patients with coronary heart disease (CHD). Methods: Cross-sectional analysis of horizontal inequities in physician-reported enrolment in the DMP for CHD in a large population-based cohort-study in Germany (2008–2010). We calculated horizontal inequity indices (HII) and their 95% confidence intervals [95%CI] for predicted need-standardised DMP enrolment across two measures of socio-economic status (SES) (educational attainment, regional deprivation) stratified by sex. Need-standardised DMP enrolment was predicted in multi-level logistic regression models. Results Among N = 1,280 individuals aged 55–84 years and diagnosed with CHD, DMP enrolment rates were 22.2% (women) and 35.0% (men). Education-related inequities in need-standardised DMP enrolment favoured groups with lower education, but HII estimates were not significant. Deprivation-related inequities among women significantly favoured groups with higher SES (HII = 0.086 [0.007 ; 0.165]. No such deprivation-related inequities were seen among men (HII = 0.014 [−0.048 ; 0.077]). Deprivation-related inequities across the whole population favoured groups with higher SES (HII estimates not significant). Conclusion: Need-standardised DMP enrolment was fairly equitable across educational levels. Deprivation-related inequities in DMP enrolment favoured women living in less deprived areas relative to those living in areas with higher deprivation. Further research is needed to gain a better understanding of the mechanisms that contribute to deprivation-related horizontal inequities in DMP enrolment among women

Risk of contralateral second primary breast cancer according to hormone receptor status in Germany

Introduction: Hormone receptor (HR) status has become an established target in treatment strategies of breast cancer. Population-based estimates of contralateral breast cancer (CBC) incidence by HR subtype in particular are limited. The aim of this study was to provide detailed data on CBC incidence for Germany. Methods: Invasive breast cancer data were extracted on 49,804 women yielding 594 second primaries from the cancer registries of the Federal States of Brandenburg and Saarland and the area of Munich for the period from 1998 to 2007. Multiple imputation was used on missing values for HR status. We estimated standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs). Results: SIR estimates of CBC among women diagnosed with an invasive first primary breast cancer (FBC) of any HR subtype ranged from 1.0 to 1.5 in the three registries. Pooling three registries' data, the SIR of HR-positive CBC was 0.7 (95% CI: 0.6 to 0.8) among women with HR-positive FBC. For those women with HR-negative FBC, the SIR of HR-negative CBC was 8.9 (95% CI: 7.1 to 11.1). Among women with FBC diagnosed before the age of 50 years, incidence of CBC was increased, especially for HR-negative FBC (SIR: 9.2; 95% CI: 7.1 to 11.9). Conclusions: HR status of the first primary and age at first diagnosis is relevant for predicting risk of CBC. Particularly, patients with HR-negative FBC had elevated risks

Survival of adults with acute lymphoblastic leukemia in Germany and the United States.

BACKGROUND: Adulthood acute lymphoblastic leukemia (ALL) is a rare disease. In contrast to childhood ALL, survival for adults with ALL is poor. Recently, new protocols, including use of pediatric protocols in young adults, have improved survival in clinical trials. Here, we examine population level survival in Germany and the United States (US) to gain insight into the extent to which changes in clinical trials have translated into better survival on the population level. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results database in the US and 11 cancer registries in Germany. Patients age 15-69 diagnosed with ALL were included. Period analysis was used to estimate 5-year relative survival (RS). RESULTS: Overall 5-year RS was estimated at 43.4% for Germany and 35.5% for the US (p = 0.004), with a decrease in survival with increasing age. Survival was higher in Germany than the US for men (43.6% versus 37.7%, p = 0.002) but not for women (42.4% versus 40.3%, p\u3e0.1). Five-year RS estimates increased in Germany and the US between 2002 and 2006 by 11.8 and 7.3 percent units, respectively (p = 0.02 and 0.04, respectively). CONCLUSIONS: Survival for adults with ALL continues to be low compared with that for children, but a substantial increase in 5-year survival estimates was seen from 2002 to 2006 in both Germany and the US. The reasons for the survival differences between both countries require clarification

The associations of DNA methylation alterations in oxidative stress-related genes with cancer incidence and mortality outcomes: a population-based cohort study

Background: Reactive oxygen species may be involved in epigenetic gene activation or silencing. We aimed to identify CpG sites, at which DNA methylation is related to urinary 8-isoprostane levels (biomarker of lipid peroxidation) and cancer or mortality outcomes. This investigation was based on a German, population-based cohort with linkage to cancer and mortality registry data (2000–2016). Results: Blood DNA methylation in promoter regions of 519 genes, known to be involved in pathways from oxidative stress (OS) to cancer, was obtained at the cohort's baseline examination. Inverse associations of DNA methylation at cg25365794 (ALOXE3) and cg08862778 (MTOR) with 8-isoprostane levels were observed in a derivation set (n = 1000) and validated in two independent subsets of the cohort (n = 548 and n = 741). Multivariate regression models were used to evaluate the associations of DNA methylation at the two CpG sites with lung, colorectal, prostate, breast, and overall cancer incidence as well as CVD, cancer, and all-cause mortality. DNA methylation at cg25365794 (ALOXE3) was inversely associated with lung and prostate cancer incidence. DNA methylation at cg08862778 (MTOR) was associated with a 43% lower breast cancer incidence in the top vs. bottom tertile. Conclusion: The finding for ALOXE3 may not be causal. As ALOXE3 is mainly expressed in skin tissue, the observed association might reflect the fact that both DNA methylation at the ALOXE3 gene and urinary 8-isoprostane concentrations depend on the level of OS in tissues. Contrarily, the finding for the MTOR gene and breast cancer is biologically plausible because the MTOR protein plays an important role in PI3K/Akt signaling, which is a pathway related to cancer development and cell senescence

Evidence for the free radical/oxidative stress theory of ageing from the CHANCES consortium : a meta-analysis of individual participant data

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-015-0537-7) contains supplementary material, which is available to authorized users

High-density lipoprotein cholesterol, coronary artery disease, and cardiovascular mortality

Aims High-density lipoprotein (HDL) cholesterol is a strong predictor of cardiovascular mortality. This work aimed to investigate whether the presence of coronary artery disease (CAD) impacts on its predictive value. Methods and results We studied 3141 participants (2191 males, 950 females) of the LUdwigshafen RIsk and Cardiovascular health (LURIC) study. They had a mean ± standard deviation age of 62.6 ± 10.6 years, body mass index of 27.5 ± 4.1 kg/m², and HDL cholesterol of 38.9 ± 10.8 mg/dL. The cohort consisted of 699 people without CAD, 1515 patients with stable CAD, and 927 patients with unstable CAD. The participants were prospectively followed for cardiovascular mortality over a median (inter-quartile range) period of 9.9 (8.7-10.7) years. A total of 590 participants died from cardiovascular diseases. High-density lipoprotein cholesterol by tertiles was inversely related to cardiovascular mortality in the entire cohort (P = 0.009). There was significant interaction between HDL cholesterol and CAD in predicting the outcome (P = 0.007). In stratified analyses, HDL cholesterol was strongly associated with cardiovascular mortality in people without CAD [3rd vs. 1st tertile: HR (95% CI) = 0.37 (0.18-0.74), P = 0.005], but not in patients with stable [3rd vs. 1st tertile: HR (95% CI) = 0.81 (0.61-1.09), P = 0.159] and unstable [3rd vs. 1st tertile: HR (95% CI) = 0.91 (0.59-1.41), P = 0.675] CAD. These results were replicated by analyses in 3413 participants of the AtheroGene cohort and 5738 participants of the ESTHER cohort, and by a meta-analysis comprising all three cohorts. Conclusion The inverse relationship of HDL cholesterol with cardiovascular mortality is weakened in patients with CAD. The usefulness of considering HDL cholesterol for cardiovascular risk stratification seems limited in such patient

German federal-state-wide seroprevalence study of 1st SARS-CoV-2 pandemic wave shows importance of long-term antibody test performance

Background Reliable data on the adult SARS-CoV-2 infection fatality rate in Germany are still scarce. We performed a federal state-wide cross-sectional seroprevalence study named SaarCoPS, that is representative for the adult population including elderly individuals and nursing home residents in the Saarland. Methods Serum was collected from 2940 adults via stationary or mobile teams during the 1st pandemic wave steady state period. We selected an antibody test system with maximal specificity, also excluding seroreversion effects due to a high longitudinal test performance. For the calculations of infection and fatality rates, we accounted for the delays of seroconversion and death after infection. Results Using a highly specific total antibody test detecting anti-SARS-CoV-2 responses over more than 180 days, we estimate an adult infection rate of 1.02% (95% CI: [0.64; 1.44]), an underreporting rate of 2.68-fold (95% CI: [1.68; 3.79]) and infection fatality rates of 2.09% (95% CI: (1.48; 3.32]) or 0.36% (95% CI: [0.25; 0.59]) in all adults including elderly individuals, or adults younger than 70 years, respectively. Conclusion The study highlights the importance of study design and test performance for seroprevalence studies, particularly when seroprevalences are low. Our results provide a valuable baseline for evaluation of future pandemic dynamics and impact of public health measures on virus spread and human health in comparison to neighbouring countries such as Luxembourg or France

Human papillomavirus vaccination of girls in the German model region Saarland: Insurance data-based analysis and identification of starting points for improving vaccination rates

In Germany, the incidence of cervical cancer, a disease caused by human papillomaviruses (HPV), is higher than in neighboring European countries. HPV vaccination has been recommended for girls since 2007. However, it continues to be significantly less well received than other childhood vaccines, so its potential for cancer prevention is not fully realized. To find new starting points for improving vaccination rates, we analyzed pseudonymized routine billing data from statutory health insurers in the PRÄZIS study (prevention of cervical carcinoma and its precursors in women in Saarland) in the federal state Saarland serving as a model region. We show that lowering the HPV vaccination age to 9 years led to more completed HPV vaccinations already in 2015. Since then, HPV vaccination rates and the proportion of 9- to 11-year-old girls among HPV-vaccinated females have steadily increased. However, HPV vaccination rates among 15-year-old girls in Saarland remained well below 50% in 2019. Pediatricians vaccinated the most girls overall, with a particularly high proportion at the recommended vaccination age of 9–14 years, while gynecologists provided more HPV catch-up vaccinations among 15-17-year-old girls, and general practitioners compensated for HPV vaccination in Saarland communities with fewer pediatricians or gynecologists. We also provide evidence for a significant association between attendance at the children´s medical check-ups “U11” or “J1” and HPV vaccination. In particular, participation in HPV vaccination is high on the day of U11. However, obstacles are that U11 is currently not financed by all statutory health insurers and there is a lack of invitation procedures for both U11 and J1, resulting in significantly lower participation rates than for the earlier U8 or U9 screenings, which are conducted exclusively with invitations and reminders. Based on our data, we propose to restructure U11 and J1 screening in Germany, with mandatory funding for U11 and organized invitations for HPV vaccination at U11 or J1 for both boys and girls