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1.  Cervical Cancer in Ethiopia: Survival of 1,059 Patients Who Received Oncologic Therapy 
The Oncologist  2014;19(7):727-734.
The primary objective was to evaluate outcome of consecutive cervical cancer patients treated over 4 years at the only radiotherapy center in Ethiopia. Two-year overall survival was 73.6%. Promoting early detection and increasing ... Increasing the capacity for external-beam radiation as well as options for brachytherapy would facilitate treatment with curative intention.
Almost 500,000 women are newly diagnosed with cervical cancer (CC) every year, the majority from developing countries. There is little information on the survival of these patients. Our primary objective was to evaluate consecutive CC patients presenting over 4 years at the only radiotherapy center in Ethiopia.
All patients with CC from September 2008 to September 2012 who received radiotherapy and/or surgery were included (without brachytherapy). Vital status was obtained through telephone contact or patient cards.
Of 2,300 CC patients, 1,059 patients with standardized treatment were included. At the end of the study, 249 patients had died; surviving patients had a median follow-up of 16.5 months; the 10% and 90% percentiles were 3.0 and 32.7 months, respectively. Mean age was 49 years (21–91 years). The majority of patients presented with International Federation of Gynecology and Obstetrics stage IIb–IIIa (46.7%). Because of progression during the waiting time (median 3.8 months), this proportion declined to 19.3% at the beginning of radiotherapy. The 1- and 2-year overall survival probabilities were 90.4% and 73.6%. If assuming a worst-case scenario (i.e., if all patients not available for follow-up after 6 months had died), the 2-year survival probability would be 45.4%.
This study gives a thorough 4-year overview of treated patients with CC in Ethiopia. Given the limited treatment availability, a relatively high proportion of patients survived 2 years. More prevention and early detection at all levels of the health care system are needed. Increasing the capacity for external-beam radiation as well as options for brachytherapy would facilitate treatment with curative intention.
PMCID: PMC4077439  PMID: 24951611
Uterine cervical neoplasms; Africa; Ethiopia; Survival; Prognosis
2.  The regional myocardial infarction registry of Saxony-Anhalt (RHESA) in Germany – rational and study protocol 
In 2012 the age-standardized acute myocardial infarction (AMI) mortality rate was in the federal state Saxony-Anhalt 67 deaths per 100.000 whereas in Germany the AMI-rate was 47 deaths per 100.000. The rate in Saxony-Anhalt was therefore 43 % above the national average. Many factors may explain this above-average AMI mortality rate:
First, the prevalence of cardiovascular risk factors (e.g. arterial hypertension, diabetes mellitus, smoking) in Saxony-Anhalt is the highest among all the Federal States of Germany. Second, structural health care for patients with AMI is potentially deficient (e.g. insufficient number of percutaneous coronary intervention-centers or deficits in the pre-hospital logistics of care). Third, the pre- and in-hospital process quality of health care for patients with AMI is possibly insufficient (e.g. time to reperfusion therapy).
In July 2013 we established the regional myocardial infarction registry of Saxony-Anhalt (Regionales Herzinfarktregister in Sachsen-Anhalt, RHESA). RHESA is a population-based registry in the eastern part of Germany.
Aims of RHESA are to calculate the AMI morbidity and mortality rates. Furthermore we study the factors that may potentially influence these rates in Saxony-Anhalt.
RHESA is a population-based registry of patients with fatal or non-fatal AMI that was established in July 2013. The registry population comprises inhabitants aged 25 years or more of the city of Halle (Saale) (n = 179.000) and inhabitants of the rural district Altmark (n = 165.000) in the federal state Saxony-Anhalt, Germany.
The main objectives of RHESA are to provide detailed estimates of the burden of AMI in Saxony-Anhalt which is the federal state with the highest AMI mortality rate in Germany and to investigate factors that influence morbidity and mortality rates due to AMI. Data collected in RHESA enable us to assess different levels of quality of health care of patients with AMI (structural, process and outcome). RHESA provides for the first time estimates of the burden of AMI in Saxony-Anhalt, and therefore contributes considerably to an improvement of the German Health Monitoring that strives for a more valid extrapolation of the nationwide morbidity and mortality rates of AMI.
Electronic supplementary material
The online version of this article (doi:10.1186/s12872-015-0040-2) contains supplementary material, which is available to authorized users.
PMCID: PMC4467162  PMID: 26054394
Myocardial infarction; Registry; Germany; Epidemiology; Cardiovascular disorders; RHESA
3.  The prevalence of estrogen receptor-negative breast cancer in Ethiopia 
BMC Cancer  2014;14:895.
In contrast with breast cancers (BCs) in other parts of the world, most previous studies reported that the majority of BCs in sub-Saharan Africa are estrogen-receptor (ER) negative. However, a recent study using the US SEER database showed that the proportion of ER-negative BC is comparable between US-born blacks and West-African born blacks but substantially lower in East African-born blacks, with over 74% of patients Ethiopians or Eritreans. In this paper, we provide the first report on the proportion of ER-negative BC in Ethiopia, and the relation to progesterone-receptor (PgR) status.
We analysed 352 female patients with ER results available out of 1208 consecutive female BC patients treated at Addis Ababa-University Hospital, Ethiopia, from June 2005 through December 2010. The influences of age, stage, and histology on the probability of ER-negative tumours were assessed by a log-linear regression model.
Of the 352 patients, only 35% were ER-negative. The proportion of ER-negative tumours decreased with advancing age at diagnosis and was not affected by histology or stage. For age, the proportion decreased by 6% for each additional 5 years (stage-adjusted prevalence ratio PR = 0.94, 95% CI: 0.89–1.00). About 31% were ER- and PgR-negative, and 69% were ER- and/or PgR-positive.
Contrary to most previous reports in other parts of sub-Saharan Africa, the majority of patients in Ethiopia are ER-positive rather than ER-negative. These findings are in line with low proportions of ER-negative BCs from East African immigrants within the SEER database, and they have clinical implications for management of BC patients in Ethiopia and other parts of sub-Saharan Africa where ER-status is not ascertained as part of routine management of the disease. Since the majority of patients showed ER-positive BC, Tamoxifen-therapy should be given to all patients even with unknown ER status.
PMCID: PMC4258259  PMID: 25433805
Breast neoplasms; Africa; Ethiopia; Prognostic factors
4.  Risk of contralateral second primary breast cancer according to hormone receptor status in Germany 
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.
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).
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).
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.
Electronic supplementary material
The online version of this article (doi:10.1186/s13058-014-0452-4) contains supplementary material, which is available to authorized users.
PMCID: PMC4303131  PMID: 25277819
5.  Renal surgery for kidney cancer in Germany 2005–2006: length of stay, risk of postoperative complications and in-hospital death 
BMC Urology  2014;14:74.
Representative statistics of surgical care among patients with kidney cancer are scant. With the introduction of the diagnosis related group system in Germany, it is now possible to provide nationwide statistics on surgical care. We studied in-hospital mortality risk in relation to comorbidity and complications, length of hospital stay in relation to surgical approach and comorbidity, and risk of complications in relation to surgical approach among kidney cancer patients undergoing nephrectomy.
We analyzed the nationwide hospitalization file of the years 2005 and 2006 including 23,753 hospitalizations with a diagnosis of renal cancer and partial or complete nephrectomy and classified comorbidity (Charlson comorbidity index) and complications. Length of stay, risk of in-hospital complications and in-hospital death were analyzed by linear regression and log-linear regression (relative risks (RR) and 95% confidence intervals (95% CI)).
The overall in-hospital mortality was 1.4%. Per one unit increase of the Charlson comorbidity index, the adjusted risk of in-hospital mortality increased by 53% (95% CI 47-59%). The risks of bleeding or acute posthaemorrhagic anemia, respiratory, urological and gastrointestinal complications and infections ranged between 1.1% and 2.7% with the exception of bleeding or acute posthaemorrhagic anemia with 18.4%. Complications were associated with an increased adjusted in-hospital mortality risk. Highest adjusted mortality risk ratios were observed for gastrointestinal (RR = 3.61, 95% CI 2.32-5.63) and urological complications (RR = 3.62, 95% CI 2.62-5.00). The risk of haemorrhage or acute posthaemorrhagic anemia was lower for total laparoscopic nephrectomies than total open nephrectomies. The adjusted risk of gastrointestinal complications was lower for partial open compared to total open nephrectomy (adjusted RR = 0.66, 95% CI 0.45-0.97). Total laparoscopic nephrectomy was associated with shorter length of stay (−3.3 days; 95% CI 2.9-3.7 days) compared to total open nephrectomy. The estimated age-adjusted increase of length of stay per one unit increase of the Charlson comorbidity index was 1.3 days (95% CI 1.2-1.4 days).
In this representative population-based analysis, we found that the surgical approach is associated with the risk of complications and length of hospital stay. Furthermore, in the era of ageing populations, renal cancer patients with comorbidities should be counseled about their increased in-hospital mortality risk.
PMCID: PMC4169703  PMID: 25217295
Hospital mortality; Intraoperative complications; Kidney cancer; Length of stay; Nephrectomy; Postoperative complications
6.  Incidence patterns and trends of gonadal and extragonadal germ cell tumors in Germany, 1998–2008 
Cancer epidemiology  2013;37(4):370-373.
Gonadal (GGCT) and extragonal germ cell tumors [GCT (EGCT)] are thought to originate from primordial germ cells. In contrast to well reported population-based data of GGCTs in males, analyses of GGCTs in females and EGCTs in both sexes remain limited.
In a pooling project of nine population-based cancer registries in Germany of the years 1998–2008, 16,883 GCTs and their topographical sites were identified using ICD-O morphology and topography for those aged 15 years and older. We estimated age-specific and age-standardized incidence rates.
Among males, the incidence of testicular GCTs increased over time. In contrast, there was no increase in the incidence of EGCTs. Among females, rates of ovarian GCTs were stable, while rates of EGCTs declined over time. The most frequent extragonadal sites were mediastinum among males and placenta among females.
Our results underline different incidence trends and distinct age-specific incidence patterns of GGCTs and EGCTs, as reported recently by several population-based registries. The differences suggest that GGCTs and EGCTs may have different etiologies.
PMCID: PMC4029332  PMID: 23683844
Extragonadal germ cell tumors; germ cell tumors; incidence; cancer registry; testicular neoplasms; ovarian neoplasms
7.  Progression of coronary artery calcification seems to be inevitable, but predictable - results of the Heinz Nixdorf Recall (HNR) study† 
European Heart Journal  2014;35(42):2960-2971.
Coronary artery calcification (CAC), as a sign of atherosclerosis, can be detected and progression quantified using computed tomography (CT). We develop a tool for predicting CAC progression.
Methods and results
In 3481 participants (45–74 years, 53.1% women) CAC percentiles at baseline (CACb) and after five years (CAC5y) were evaluated, demonstrating progression along gender-specific percentiles, which showed exponentially shaped age-dependence. Using quantile regression on the log-scale (log(CACb+1)) we developed a tool to individually predict CAC5y, and compared to observed CAC5y. The difference between observed and predicted CAC5y (log-scale, mean±SD) was 0.08±1.11 and 0.06±1.29 in men and women. Agreement reached a kappa-value of 0.746 (95% confidence interval: 0.732–0.760) and concordance correlation (log-scale) of 0.886 (0.879–0.893). Explained variance of observed by predicted log(CAC5y+1) was 80.1% and 72.0% in men and women, and 81.0 and 73.6% including baseline risk factors. Evaluating the tool in 1940 individuals with CACb>0 and CACb<400 at baseline, of whom 242 (12.5%) developed CAC5y>400, yielded a sensitivity of 59.5%, specificity 96.1%, (+) and (−) predictive values of 68.3% and 94.3%. A pre-defined acceptance range around predicted CAC5y contained 68.1% of observed CAC5y; only 20% were expected by chance. Age, blood pressure, lipid-lowering medication, diabetes, and smoking contributed to progression above the acceptance range in men and, excepting age, in women.
CAC nearly inevitably progresses with limited influence of cardiovascular risk factors. This allowed the development of a mathematical tool for prediction of individual CAC progression, enabling anticipation of the age when CAC thresholds of high risk are reached.
PMCID: PMC4223611  PMID: 25062951
Coronary artery calcification; Progression of atherosclerosis; CT; Imaging; Heinz Nixdorf Recall study; Epidemiology
8.  A novel approach for estimating the nationwide incidence of renal cancer 
The aim of this study was to provide a novel approach for estimating the incidence of renal cancer in Germany by using hospitalization data from the years 2005–2006 and to compare these estimates with incidence rates from cancer registries.
We used nationwide hospitalization data from the years 2005–2006 including 34.2 million hospitalizations. We used three definitions of potential incident renal cancer cases: 1) a main or secondary diagnosis of renal cancer and a partial or total nephrectomy; 2) a main diagnosis of renal cancer and a partial or total nephrectomy; and 3) a main diagnosis of renal cancer (without a secondary diagnosis of renal pelvis cancer) and a partial or total nephrectomy. In addition, we used cancer registry data for comparison of rates.
Hospitalization data to which definition 2 applied provided incidence rate estimates nearly identical to those provided by the cancer registries (when the cases registered from death certificates only were excluded). Age-standardized (European standard population) incidence rates based on hospitalization data and cancer registry data were 15.6 per 100 000 and 15.7 per 100 000 among men and 8.0 per 100 000 and 7.6 per 100 000 among women respectively. Cancer registry-based incidence rates were lower especially among those federal states with an estimated completeness of registration below 90% (Berlin and Saxony-Anhalt).
Representative hospitalization data can be used to estimate incidence rates of renal cancer. We propose that incidence rates can be estimated by hospitalization data if 1) the primary treatment is performed during an in-hospital stay and 2) nearly all patients undergo a defined surgical procedure that is not repeated for the treatment of the same cancer. Our results may be useful for countries with no or incomplete cancer registration or for countries that use hospitalization data to provide a representative incidence of renal cancer.
PMCID: PMC4108273  PMID: 25057278
Kidney neoplasms; Incidence; Registries; Hospitalization; Nephrectomy
9.  Assessment of the effect of iris colour and having children on 5-year risk of death after diagnosis of uveal melanoma: a follow-up study 
BMC Ophthalmology  2014;14:42.
To examine the all-cause mortality and uveal melanoma specific mortality among newly diagnosed uveal melanoma patients after five years. Furthermore, we assess of the effect of iris colour and having children on 5-year risk of death after diagnosis of uveal melanoma. Therefore, we assess the performance of an individual prediction model of survival from uveal melanoma.
A cohort of 459 patients aged 45 to 79 years with newly diagnosed uveal melanoma was recruited between 2002 and 2004 from the Division of Ophthalmology, University of Essen, Germany. Survival probabilities were estimated by Kaplan-Meier survival analysis. The clinical and histopathological characteristics were obtained from medical records. Iris colour and childbearing history were assessed at baseline by a computer-assisted telephone interview. We used crude and multivariable Cox proportional hazards regression to estimate unadjusted and adjusted hazard ratios (HR) and corresponding 95% confidence intervals (95%CIs) with respect to death from uveal melanoma and death from all causes. We used the Cox model to estimate adjusted probabilities of primary events. For computing Harrell’s C statistics, we used a Cox model including the prognostics factors gender, age at diagnosis, ciliary body involvement, largest basal tumour diameter, and iris colour.
The 5-year uveal melanoma-specific survival probability was 82.9% (95% CI: 79.1-86.3). Main prognostic factors for the death of uveal melanoma were ciliary body involvement (HR: 1.7 (95% CI:1.0-2.8)), largest basal tumour diameter >15 mm HR: 7.0 (95% CI: 3.5-13.9), light iris colour (HR: 2.3 (95% CI: 0.9-5.8), having children (HR: 0.6 (95% CI: 0.2 - 1.7)), and gender (HR: 0.7 (95% CI: 0.4-1.1)). The value of the bootstrap-corrected C statistics was 0.76 (95% CI: 0.74-0.77).
Beyond the established prognostic factors, light iris colour also appears to be a prognostic factor for death from uveal melanoma.
PMCID: PMC3998741  PMID: 24685257
Uveal melanoma; Prognostic factors; Follow-up study; Iris colour; Children
10.  Risk of second primary cancers after testicular cancer in East and West Germany: A focus on contralateral testicular cancers 
Asian Journal of Andrology  2014;16(2):285-289.
Testicular cancer survival rates improved dramatically after cisplatin-based therapy was introduced in the 1970s. However, chemotherapy and radiation therapy are potentially carcinogenic. The purpose of this study was to estimate the risk of developing second primary cancers including the risk associated with primary histologic type (seminoma and non-seminoma) among testicular cancer survivors in Germany. We identified 16 990 and 1401 cases of testicular cancer in population-based cancer registries of East Germany (1961–1989 and 1996–2008) and Saarland (a federal state in West Germany; 1970–2008), respectively. We estimated the risk of a second primary cancer using standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs). To determine trends, we plotted model-based estimated annual SIRs. In East Germany, a total of 301 second primary cancers of any location were observed between 1961 and 1989 (SIR: 1.9; 95% CI: 1.7–2.1), and 159 cancers (any location) were observed between 1996 and 2008 (SIR: 1.7; 95% CI: 1.4–2.0). The SIRs for contralateral testicular cancer were increased in the registries with a range from 6.0 in Saarland to 13.9 in East Germany. The SIR for seminoma, in particular, was higher in East Germany compared to the other registries. We observed constant trends in the model-based SIRs for contralateral testicular cancers. The majority of reported SIRs of other cancer sites including histology-specific risks showed low precisions of estimated effects, likely due to small sample sizes. Testicular cancer patients are at increased risk especially for cancers of the contralateral testis and should receive intensive follow-ups.
PMCID: PMC3955342  PMID: 24407180
cancer registry; incidence; neoplasms; second primary; testicular neoplasms
11.  Educational level, prevalence of hysterectomy, and age at amenorrhoea: a cross-sectional analysis of 9536 women from six population-based cohort studies in Germany 
BMC Women's Health  2014;14:10.
Hysterectomy prevalence has been shown to vary by education level. Hysterectomy influences age at amenorrhoea. The aim of this study was to examine these associations in Germany within population-based data sets.
Baseline assessments in six population-based cohorts took place from 1997 through 2006 and included 9,548 women aged 20–84 years. All studies assessed hysterectomy history, school and professional degrees. Degrees were categorized into three levels each. Adjusted prevalence ratios and 95% confidence intervals (95% CI) were estimated.
Prevalences were higher in West Germany than East Germany, increased by age, and leveled off starting at 55–64 years. The age- and study-adjusted prevalence ratio (lowest versus highest school level) was 2.61 (95% CI: 1.28-5.30), 1.48 (95% CI: 1.21-1.81), and 1.01 (95% CI: 0.80-1.28) for women aged 20–45, 45–64, and 65 and more years respectively. The estimated adjusted prevalence ratios per one unit decrement of the educational qualification score (range 1 = lowest, 8 = highest) were 1.29 (95% CI: 1.02-1.64), 1.08 (95% CI: 1.04-1.12), and 0.98 (95% CI: 0.93-1.03) for women aged 20–44, 45–64, and 65–84 years respectively. Age at amenorrhoea was on average 6.2 years lower (43.5 years versus 49.7 years) among women with a history of hysterectomy than those without.
Lower educational level was associated with a higher hysterectomy prevalence among women aged 20–64 years. Several mediators associated with educational level and hysterectomy including women’s disease risk, women’s treatment preference, and women’s access to uterus-preserving treatment may explain this association. At population level, hysterectomy decreases the age of amenorrhoea on average by 6.2 years.
PMCID: PMC3898063  PMID: 24433474
Hysterectomy; Population surveillance; Prevalence; Education; Amenorrhoea
12.  A population-based case–control study on social factors and risk of testicular germ cell tumours 
BMJ Open  2013;3(9):e003833.
Incidence rates for testicular cancer have risen over the last few decades. Findings of an association between the risk of testicular cancer and social factors are controversial. The association of testicular cancer and different indicators of social factors were examined in this study.
Case–control study.
Population-based multicentre study in four German regions (city states Bremen and Hamburg, the Saarland region and the city of Essen).
The study included 797 control participants and 266 participants newly diagnosed with testicular cancer of which 167 cases were classified as seminoma and 99 as non-seminoma. The age of study participants ranged from 15 to 69 years.
Social position was classified by educational attainment level, posteducational training, occupational sectors according to Erikson-Goldthorpe-Portocarrero (EGP) and the socioeconomic status (SES) on the basis of the International SocioEconomic Index of occupational status (ISEI). ORs and corresponding 95% CIs (95% CIs) were calculated for the whole study sample and for seminoma and non-seminoma separately.
Testicular cancer risk was modestly increased among participants with an apprenticeship (OR=1.7 (95% CI 1.0 to 2.8)) or a university degree (OR=1.6 (95% CI 0.9 to 2.8)) relative to those whose education was limited to school. Analysis of occupational sectors revealed an excess risk for farmers and farm-related occupations. No clear trend was observed for the analyses according to the ISEI-scale.
Social factors based on occupational measures were not a risk factor for testicular cancer in this study. The elevated risk in farmers and farm-related occupations warrants further research including analysis of occupational exposures.
PMCID: PMC3780297  PMID: 24056494
13.  Population-based incidences of non-fatal injuries - results of the German-wide telephone survey 2004 
BMC Public Health  2013;13:376.
To plan preventive measures against accident-related injuries, it is important to have detailed epidemiological data on this topic. The aim of this report was to present population-based incidence estimates of injuries due to non-fatal accidents in relation to age, gender and educational level.
We performed a cross-sectional telephone survey from 2003 to 2004 of the resident adult population of Germany, which included 7,341 subjects (response rate: 32.6 to 39.4%). The interview included 13 questions about injuries caused by accidents that happened in the 12 months preceding the interview. We estimated one-year cumulative incidences of injuries by gender, age and educational level.
Overall, 10.3% of the subjects reported an unintentional injury requiring medical treatment in the previous 12 months. The age-standardised incidence of injuries was higher among men than women (men: 11.3%, women: 8.9%). Generally, accidents at home were the most frequently reported (27.4%). Men and women aged 18 to 29 years suffered accident-related injuries (and also repeated injuries) the most often during the preceding 12 months.
Although the overall incidence of injuries caused by accidents did not differ by educational level, the incidences of accidents at different places differed by educational level. The incidence of work-related injuries was higher among people with a low educational level.
Our age- and gender-specific results provide detailed insight into specific patterns of accident-related injuries in Germany. Young men are especially at high risk of injuries. This information is valuable because a nationwide comprehensive recording of injuries caused by accidents does not exist. The data highlight the target groups for injury prevention measures.
PMCID: PMC3641992  PMID: 23607782
Epidemiology; Germany; Injuries; Accidents; Traffic accidents; Domestic accidents; Leisure-time accidents; Work-related accidents; Incidence; Health survey
14.  Mammographic density and inter-observer variability of pathologic evaluation of core biopsies among women with mammographic abnormalities 
BMC Cancer  2012;12:554.
As high percentage of mammographic densities complicates the assessment of imaging findings, mammographic density may influence the histopathological evaluation of core-biopsies of the breast. We measured the influence of mammographic density on the inter-observer variability of histopathological findings of breast biopsies.
Histological slides of 695 women who underwent core biopsies of the breast at University of Halle between 2006 and 2008 were evaluated in a blinded fashion by two pathologists using the five levels of the B-categorization scheme (B1-B5). To quantify mammographic density, we used a computer-based threshold method (Madena). We calculated observed and chance-corrected agreements (weighted kappa) and 95% confidence intervals (95% CI) according to four categories of mammographic density (<10%, 10<25%, 25<50%, ≥50%).
The weighted kappa decreased monotonically from 89.6% (95% CI: 85.8%, 93.3%) among women with less than 10% of mammographic density to 80.4% (95% CI: 69.9%, 90.9%) for women with more than 50% of mammographic density, respectively. Results of a kappa regression analysis showed that agreement of pathologists on clinically relevant categories (B1-B2 versus B3-B5) decreased with mammographic density.
Mammographic density is a relevant modifier of the agreement between pathologists who assess breast biopsies using the B-categorization scheme. The influence of mammographic density on the inter-observer variability can be explained to some extent by varying prevalences of histological entities across B categories that have typically different inter-observer agreement. Women with high mammographic density are at higher risk of inter-observer variability compared to women with low mammographic density and should possibly undergo a second pathology review.
PMCID: PMC3529189  PMID: 23176326
Biopsy; Breast diseases; Mammographic density; Observer variation
15.  Insomnia and urban neighbourhood contexts – are associations modified by individual social characteristics and change of residence? Results from a population-based study using residential histories 
BMC Public Health  2012;12:810.
Until now, insomnia has not been much of interest in epidemiological neighbourhood studies, although literature provides evidence enough for insomnia-related mechanisms being potentially dependent on neighbourhood contexts. Besides, studies have shown differences in sleep along individual social characteristics that might render residents more vulnerable to neighbourhood contextual exposures. Given the role of exposure duration and changes in the relationship between neighbourhoods and health, we studied associations of neighbourhood unemployment and months under residential turnover with insomnia by covering ten years of residential history of nearly 3,000 urban residents in the Ruhr Area, Germany.
Individual data were retrieved from the Heinz Nixdorf Recall Study, a population-based study of randomly chosen participants from adjacent cities, which contains self-rated insomnia symptoms and individual social characteristics. Participants’ residential addresses were retrospectively assessed using public registries. We built individually derived exposure measures informing about mean neighbourhood unemployment rates and months under high residential turnover. These measures were major predictors in multivariate logistic regressions modelling the association between social neighbourhood characteristics and insomnia in the whole sample and subgroups defined by low income, low education, social isolation, and change of residence. Traffic-related noise, age, gender, economic activity, and education were considered as covariates.
Nearly 12 per cent of the participants complained about insomnia. Associations of neighbourhood unemployment with insomnia were more consistent than those of residential turnover in the whole sample (adjusted OR 1.42, 95% CI 1.00-2.03 for neighbourhood unemployment and OR 1.33, 95% CI 0.78-2.25 for residential turnover in the highest exposure categories). In low-income and socially isolated participants, neighbourhood unemployment odds of reporting insomnia were particularly elevated (adjusted OR 2.90, 95% CI 1.39-6.02 and OR 3.32, 95% CI 1.11-9.96, respectively). Less educated participants displayed relatively high odds of reporting insomnia throughout all upper neighbourhood unemployment exposure categories. Change of residence weakened associations, whereas undisrupted exposure sharpened them by trend.
Our findings hint at multiple stressors being effective in both the neighbourhood context and individual resident, possibly reflecting precarious life situations undermining residents’ sleep and health chances. Moreover, our results suggest a temporal dependency in the association between neighbourhood and insomnia.
PMCID: PMC3503830  PMID: 22994885
Insomnia; Neighbourhood unemployment; Residential turnover; Income; Education; Social isolation; Change of residence.
16.  Impact of classification of mixed germ cell tumors on incidence trends of nonseminoma 
International journal of andrology  2011;34(4 Pt 2):e274-e277.
Seminomas and nonseminomas (embryonal carcinomas, yolk sac tumors, teratomas, choriocarcinomas, mixed germ cell tumors) are the major histologic types of testicular germ cell tumors (TGCT). TGCTs composed of both seminomatous and nonseminomatous elements have been coded as their nonseminoma component in the World Health Organization (WHO) classification. In the late 1980's, a provisional International Classification of Diseases for Oncology (ICD-O) morphology code for mixed germ cell tumors was introduced. Using data from the Surveillance, Epidemiology and End Results (SEER) Program and two population-based German cancer registries, we examined the impact of MGCT classification on TGCT trends. Cases were identified using ICD-O topography (ICD-9: 186; ICD-10: C62) and morphology codes (seminoma = 9060-9062, 9064; embryonal carcinoma = 9070; yolk sack tumor = 9071; teratoma = 9080-9084, 9102; choriocarcinoma = 9100, 9101; MGCT = 9085; all nonseminoma = 9065-9102). As MGCTs and teratoma are often grouped as a single histologic group, we analyzed teratoma both including and excluding MGCTs. Between 1988 and 2007, incidence rates of MGCT in the U.S. increased 407%. Rates of teratoma including MGCT increased 80% while rates of teratoma excluding MGCT decreased 71%. Rates of embryonal carcinoma [-40%] and choriocarcinoma [-22%] also declined, suggesting that the code for MGCT is now being used for any mixed histology. Similar declines in incidence were observed in the German comparison populations. The declines in incidence of teratoma (excluding MGCT), embryonal carcinoma and choriocarcinoma in the US data since 1988 are likely due, in part, to increases in classifying any TGCT with mixed histology as MGCT. These results suggest that analysis of trends in specific histologic types of nonseminoma should be interpreted cautiously.
PMCID: PMC3145003  PMID: 21623833
testicular germ cell tumors; mixed germ cell tumors; histology; incident trends
17.  Prevention and health promotion in undergraduate medical education: Preferences, attitudes and previous knowledge of medical students - a cross-sectional study 
Objective: The interdisciplinary topic "prevention and health promotion" (Q10) was introduced into the medical training in Germany by the new medical licensing regulations in 2004. For the conception of an effective curriculum, it is helpful to know student preferences concerning teaching-formats, attitudes and self-estimated previous knowledge. Little is known concerning student perception of “prevention and health promotion” in Germany. Thus, this explorative cross-sectional study aims to provide a first step for closing this gap.
Methods: Medical students (n=220) in the fifth academic year were asked to fill in a standardized questionnaire prior to the Q10 curriculum. Questions focused on preferences for teaching and testing formats and self-estimated previous knowledge as well as on rating the importance of prevention topics and health risks. The questions were multiple choice, five-point Likert scales and open-ended questions.
Results: A total of 94 students filled questionnaires (42% response rate). Prevention and health promotion was rated as “important” or “very important” for their “own medical professionalism” by 68% of students. Ratings showed preferences for self-directed teaching and learning strategies, including case-based learning, and 78% wished for predominantly oral examinations. The self-estimated knowledge about prevention and health promotion is rated as “rather poor”. The most favored training aim was “decision making within the physician-patient-relationship”. Regarding medical health consultation, students frequently estimate “lifestyle factors” and “psychological disease” as being "very important".
Conclusion: Students’ self-estimated poor previous knowledge of prevention and health promotion creates special challenges for curriculum development. High ratings of relevance assigned to prevention-related topics point to a motivational potential which should be utilized through suitable selection of teaching and testing formats to achieve effective and practice-relevant instructional content.
PMCID: PMC3140399  PMID: 21818232
Curriculum; health promotion; prevention; interdisciplinary teaching; evaluation
18.  A case-control study: occupational cooking and the risk of uveal melanoma 
BMC Ophthalmology  2010;10:26.
A European-wide population based case-control study (European rare cancer study) undertaken in nine European countries examined risk factors for uveal melanoma. They found a positive association between cooks and the risk of uveal melanoma. In our study we examine whether cooks or people who worked in cook related jobs have an increased uveal melanoma risk.
We conducted a case-control study during 2002 and 2005. Overall, 1653 eligible subjects (age range: 20-74 years, living in Germany) participated. Interviews were conducted with 459 incident uveal melanoma cases, 827 population controls, 180 ophthalmologist controls and 187 sibling controls. Data on occupational exposure were obtained from a self-administered postal questionnaire and a computer-assisted telephone interview. We used conditional logistic regression to estimate odds ratios adjusting for the matching factors.
Overall, we did not observe an increased risk of uveal melanoma among people who worked as cooks or who worked in cook related jobs. When we restricted the source population of our study to the population of the Federal State of Northrhine-Westphalia, we observed an increased risk among subjects who were categorized as cooks in the cases-control analysis.
Our results are in conflict with former results of the European rare cancer study. Considering the rarity of the disease laboratory in vitro studies of human uveal melanoma cell lines should be done to analyze potential exposure risk factors like radiation from microwaves, strong light from incandescent ovens, or infrared radiation.
PMCID: PMC2978138  PMID: 20969762
19.  Compliance assessment of ambulatory Alzheimer patients to aid therapeutic decisions by healthcare professionals 
Compliance represents a major determinant for the effectiveness of pharmacotherapy. Compliance reports summarising electronically compiled compliance data qualify healthcare needs and can be utilised as part of a compliance enhancing intervention. Nevertheless, evidence-based information on a sufficient level of compliance is scarce complicating the interpretation of compliance reports. The purpose of our pilot study was to determine the compliance of ambulatory Alzheimer patients to antidementia drugs under routine therapeutic use using electronic monitoring. In addition, the forgiveness of donepezil (i.e. its ability to sustain adequate pharmacological response despite suboptimal compliance) was characterised and evidence-based guidance for the interpretation of compliance reports was intended to be developed.
We determined the compliance of four different antidementia drugs by electronic monitoring in 31 patients over six months. All patients were recruited from the gerontopsychiatric clinic of a university hospital as part of a pilot study. The so called medication event monitoring system (MEMS) was employed, consisting of a vial with a microprocessor in the lid which records the time (date, hour, minute) of every opening. Daily compliance served as primary outcome measure, defined as percentage of days with correctly administered doses of medication. In addition, pharmacokinetics and pharmacodynamics of donepezil were simulated to systematically assess therapeutic undersupply also incorporating study compliance patterns. Statistical analyses were performed with SPSS and Microsoft Excel.
Median daily compliance was 94% (range 48%-99%). Ten patients (32%) were non-compliant at least for one month. One-sixth of patients taking donepezil displayed periods of therapeutic undersupply. For 10 mg and 5 mg donepezil once-daily dosing, the estimated forgiveness of donepezil was 80% and 90% daily compliance or two and one dosage omissions at steady state, respectively. Based on the simulation findings we developed rules for the evidence-based interpretation of donepezil compliance reports.
Compliance in ambulatory Alzheimer patients was for the first time assessed under routine conditions using electronic monitoring: On average compliance was relatively high but variable between patients. The approach of pharmacokinetic/pharmacodynamic in silico simulations was suitable to characterise the forgiveness of donepezil suggesting evidence-based recommendations for the interpretation of compliance reports.
PMCID: PMC2928215  PMID: 20696034
20.  The Epidemiology and Aetiology of Female Breast Cancer 
Breast Care  2009;4(2):73-74.
PMCID: PMC2931063  PMID: 20847882
21.  Chronic Residential Exposure to Particulate Matter Air Pollution and Systemic Inflammatory Markers 
Environmental Health Perspectives  2009;117(8):1302-1308.
Long-term exposure to urban air pollution may accelerate atherogenesis, but mechanisms are still unclear. The induction of a low-grade systemic inflammatory state is a plausible mechanistic pathway. Objectives: We analyzed the association of residential long-term exposure to particulate matter (PM) and high traffic with systemic inflammatory markers.
We used baseline data from the German Heinz Nixdorf Recall Study, a population-based, prospective cohort study of 4,814 participants that started in 2000. Fine PM [aerodynamic diameter ≤ 2.5 μm (PM2.5)] exposure based on a small-scale dispersion and chemistry transport model was assigned to each home address. We calculated distances between residences and major roads. Long-term exposure to air pollution (annual PM2.5 and distance to high traffic) and concentration of inflammatory markers [high-sensitivity C-reactive protein (hs-CRP) and fibrinogen] on the day of the baseline visit were analyzed with sex-stratified multiple linear regression, controlling for individual-level risk factors.
In the adjusted analysis, a cross-sectional exposure difference of 3.91 μg/m3 in PM2.5 (interdecile range) was associated with increases in hs-CRP of 23.9% [95% confidence interval (CI), 4.1 to 47.4%] and fibrinogen of 3.9% (95% CI, 0.3 to 7.7%) in men, whereas we found no association in women. Chronic traffic exposure was not associated with inflammatory markers. Short-term exposures to air pollutants and temperature did not influence the results markedly.
Our study indicates that long-term residential exposure to high levels of PM2.5 is associated with systemic inflammatory markers in men. This might provide a link between air pollution and coronary atherosclerosis.
PMCID: PMC2721876  PMID: 19672412
air quality; cardiovascular disease; epidemiology; inflammation; roadway proximity
22.  Mobile Phone Use and Risk of Uveal Melanoma: Results of the Risk Factors for Uveal Melanoma Case-Control Study 
We recently reported an increased risk of uveal melanoma among mobile phone users. Here, we present the results of a case–control study that assessed the association between mobile phone use and risk of uveal melanoma. We recruited 459 uveal melanoma case patients at the University of Duisburg-Essen and matched 455 case patients with 827 population control subjects, 133 with 180 ophthalmologist control subjects, and 187 with 187 sibling control subjects. We used a questionnaire to assess mobile phone use and estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) of risk for uveal melanoma using conditional logistic regression. Risk of uveal melanoma was not associated with regular mobile phone use (OR = 0.7, 95% CI = 0.5 to 1.0 vs population control subjects; OR = 1.1, 95% CI = 0.6 to 2.3 vs ophthalmologist control subjects; and OR = 1.2, 95% CI = 0.5 to 2.6 vs sibling control subjects), and we observed no trend for cumulative measures of exposure. We did not corroborate our previous results that showed an increased risk of uveal melanoma among regular mobile phone users.
PMCID: PMC2639317  PMID: 19141780
23.  Comparison of Subclinical Coronary Atherosclerosis and Risk Factors in Unselected Populations in Germany and US-America 
Atherosclerosis  2007;195(1):e207-e216.
On the basis of the Framingham risk algorithm, overestimation of clinical events has been reported in some European populations. Electron-beam computed tomography-derived quantification of coronary artery calcification (CAC) allows for noninvasive assessment of coronary atherosclerosis in the general population and may thus add important in vivo information on the path from risk factor exposure to formation of clinical events. The current study was undertaken to compare the relationship between risk factors and subclinical coronary atherosclerosis between non-Hispanic white cohorts in Germany and US-America, the hypothesis being that subclinical coronary atherosclerosis might be less prevalent in Europe at the same level of classical risk factor exposure.
The Heinz Nixdorf Recall (HNR) study, conducted in the German Ruhr area and the Epidemiology of Coronary Calcification (ECAC) study, conducted in Olmsted County, Minnesota, both recruited large unselected cohorts, men and women aged 45 – 74 years, from the general population. All subjects with no history of coronary artery disease (CAD) or stroke were included (n = 3,120 in HNR, n = 703 in ECAC). Coronary risk factors were assessed by personal and computer-assisted interviews and direct laboratory measurements. Cardiovascular medication use (antihypertensive, lipid-lowering, and anti-diabetic) was noted. CAC scores were determined using the Agatston method in an identical fashion in both studies.
Adverse levels of risk factors were more prevalent, and the Framingham risk score was higher (10.6 ± 7.6 vs. 9.3 ± 7.1, p < 0.001) in HNR than ECAC, respectively. There was no difference in body mass index (BMI). CAC scores were greater in HNR than in ECAC (mean values, 155.7 ± 423.0 versus 107.2 ± 280.0; median values, 11.9 versus 2.4; p < 0.001, respectively). When subjects were matched on CAD risk factors, presence and quantity of CAC were similar in the 2 cohorts. Risk factors significantly associated with CAC score in both studies included: age, male sex, current and former smoking, systolic blood pressure, and non HDL-cholesterol. Inferences were similar after excluding subjects using lipid- or blood pressure-lowering medications. Using the same risk factor variables for modelling, the predicted CAC scores were comparable in both cohorts.
In the higher-risk German cohort, presence and quantity of CAC were greater than in the lower-risk US-American cohort. Risk factor associations, however, with CAC were very similar in both unselected populations. As opposed to studies concerning clinical endpoints, we could not demonstrate a relative increase in subclinical coronary atherosclerosis in the US-American cohort.
PMCID: PMC2293130  PMID: 17532322
24.  Signs of subclinical coronary atherosclerosis in relation to risk factor distribution in the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR) 
European Heart Journal  2008;29(22):2782-2791.
Modern imaging technology allows us the visualization of coronary artery calcification (CAC), a marker of subclinical coronary atherosclerosis. The prevalence, quantity, and risk factors for CAC were compared between two studies with similar imaging protocols but different source populations: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR).
Methods and results
The measured CAC in 2220 MESA participants were compared with those in 3126 HNR participants with the inclusion criteria such as age 45–75 years, Caucasian race, and free of baseline cardiovascular disease. Despite similar mean levels of CAC of 244.6 among participants in MESA and of 240.3 in HNR (P = 0.91), the prevalence of CAC > 0 was lower in MESA (52.6%) compared with HNR (67.0%) with a prevalence rate ratio of CAC > 0 of 0.78 [95% confidence interval (CI): 0.72–0.85] after adjustment for known risk factors. Consequently, among participants with CAC > 0, the participants in MESA tended to have higher levels of CAC than those in HNR (ratio of CAC levels: 1.39; 95% CI: 1.19–1.63), since many HNR participants have small (near zero) CAC values.
The CAC prevalence was lower in the United States (MESA) cohort than in the German (HNR) cohort, which may be explained by more favourable risk factor levels among the MESA participants. The predictors for increased levels of CAC were, however, similar in both cohorts with the exception that male gender, blood pressure, and body mass index were more strongly associated in the HNR cohort.
PMCID: PMC2582985  PMID: 18845666
Epidemiology; Atherosclerosis; Coronary artery calcium; Risk factors; Screening
25.  Low socio-economic position is associated with poor social networks and social support: results from the Heinz Nixdorf Recall Study 
Social networks and social support are supposed to contribute to the development of unequal health within populations. However, little is known about their socio-economic distribution. In this study, we explore this distribution.
This study analyses the association of two indicators of socio-economic position, education and income, with different measures of social networks and support. Cross-sectional data have been derived from the baseline examination of an epidemiological cohort study of 4.814 middle aged urban inhabitants in Germany (Heinz Nixdorf Recall Study). Bivariate and multivariate logistic regression analysis were carried out to estimate the risk of having poor social networks and support across socio-economic groups.
Socially disadvantaged persons more often report poor social networks and social support. In multivariate analyses, based on education, odds ratios range from 1.0 (highest education) to 4.9 (lowest education) in a graded way. Findings based on income show similar effects, ranging from 1.0 to 2.5. There is one exception: no association of SEP with close ties living nearby and regularly seen was observed.
Poor social networks and low social support are more frequent among socio-economically disadvantaged people. To some extent, this finding varies according to the indicator chosen to measure these social constructs.
PMCID: PMC2424055  PMID: 18457583

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