Publications by authors named "Daniel Medenwald"

40 Publications

Trends in radiotherapy inpatient admissions in Germany: a population-based study over a 10-year period.

Strahlenther Onkol 2021 Oct 3;197(10):865-875. Epub 2021 Sep 3.

Department of Radiation Oncology, University Hospital Halle (Saale), Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany.

Objective: With the increasing complexity of oncological therapy, the number of inpatient admissions to radiotherapy and non-radiotherapy departments might have changed. In this study, we aim to quantify the number of inpatient cases and the number of radiotherapy fractions delivered under inpatient conditions in radiotherapy and non-radiotherapy departments.

Methods: The analysis is founded on data of all hospitalized cases in Germany based on Diagnosis-Related Group Statistics (G-DRG Statistics, delivered by the Research Data Centers of the Federal Statistical Office). The dataset includes information on the main diagnosis of cases (rather than patients) and the performed procedures during hospitalization based on claims of reimbursement. We used linear regression models to analyze temporal trends. The considered data encompass the period from 2008 to 2017.

Results: Overall, the number of patients treated with radiotherapy as inpatients remained constant between 2008 (N = 90,952) and 2017 (N = 88,998). Starting in January 2008, 48.9% of 4000 monthly cases received their treatment solely in a radiation oncology department. This figure decreased to 43.7% of 2971 monthly cases in October 2017. We found a stepwise decrease between December 2011 and January 2012 amounting to 4.3%. Fractions received in radiotherapy departments decreased slightly by 29.3 (95% CI: 14.0-44.5) fractions per month. The number of days hospitalized in radiotherapy departments decreased by 83.4 (95% CI: 59.7, 107.0) days per month, starting from a total of 64,842 days in January 2008 to 41,254 days in 2017. Days per case decreased from 16.2 in January 2008 to 13.9 days in October 2017.

Conclusion: Our data give evidence to the notion that radiotherapy remains a discipline with an important inpatient component. Respecting reimbursement measures and despite older patients with more comorbidities, radiotherapy institutions could sustain a constant number of cases with limited temporal shifts.
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http://dx.doi.org/10.1007/s00066-021-01829-7DOI Listing
October 2021

Hsp70 in Liquid Biopsies-A Tumor-Specific Biomarker for Detection and Response Monitoring in Cancer.

Cancers (Basel) 2021 Jul 23;13(15). Epub 2021 Jul 23.

Center for Translational Cancer Research (TranslaTUM), Radiation Immuno-Oncology Group, Technical University of Munich (TUM), Klinikum rechts der Isar, Einsteinstr. 25, 81675 Munich, Germany.

In contrast to normal cells, tumor cells of multiple entities overexpress the Heat shock protein 70 (Hsp70) not only in the cytosol, but also present it on their plasma membrane in a tumor-specific manner. Furthermore, membrane Hsp70-positive tumor cells actively release Hsp70 in small extracellular vesicles with biophysical characteristics of exosomes. Due to conformational changes of Hsp70 in a lipid environment, most commercially available antibodies fail to detect membrane-bound and vesicular Hsp70. To fill this gap and to assess the role of vesicular Hsp70 in circulation as a potential tumor biomarker, we established the novel complete (comp)Hsp70 sandwich ELISA, using two monoclonal antibodies (mAbs), that is able to recognize both free and lipid-associated Hsp70 on the cell surface of viable tumor cells and on small extracellular vesicles. The epitopes of the mAbs cmHsp70.1 (aa 451-461) and cmHsp70.2 (aa 614-623) that are conserved among different species reside in the substrate-binding domain of Hsp70 with measured affinities of 0.42 nM and 0.44 nM, respectively. Validation of the compHsp70 ELISA revealed a high intra- and inter-assay precision, linearity in a concentration range of 1.56 to 25 ng/mL, high recovery rates of spiked liposomal Hsp70 (>84%), comparable values between human serum and plasma samples and no interference by food intake or age of the donors. Hsp70 concentrations in the circulation of patients with glioblastoma, squamous cell or adeno non-small cell lung carcinoma (NSCLC) at diagnosis were significantly higher than those of healthy donors. Hsp70 concentrations dropped concomitantly with a decrease in viable tumor mass upon irradiation of patients with approximately 20 Gy (range 18-22.5 Gy) and after completion of radiotherapy (60-70 Gy). In summary, the compHsp70 ELISA presented herein provides a sensitive and reliable tool for measuring free and vesicular Hsp70 in liquid biopsies of tumor patients, levels of which can be used as a tumor-specific biomarker, for risk assessment (i.e., differentiation of grade III vs. IV adeno NSCLC) and monitoring of therapeutic outcomes.
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http://dx.doi.org/10.3390/cancers13153706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345117PMC
July 2021

Presentation, patterns of care, and outcomes of patients with prostate cancer in sub-Saharan Africa: A population-based registry study.

Cancer 2021 Jul 30. Epub 2021 Jul 30.

Institute of Medical Epidemiology, Biometrics and Informatics, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.

Background: Although prostate cancer (PCa) is the most commonly diagnosed cancer in men of sub-Saharan Africa (SSA), little is known about its management and survival. The objective of the current study was to describe the presentation, patterns of diagnosis, treatment, and survival of patients with PCa in 10 countries of SSA.

Methods: In this observational registry study with data collection from 2010 to 2018, the authors drew a random sample of 738 patients with PCa who were registered in 11 population-based cancer registries. They described proportions of patients receiving recommended care and presented survival estimates. Multivariable Cox regression was used to calculate hazard ratios comparing the survival of patients with and without cancer-directed therapies (CDTs).

Results: The study included 693 patients, and tumor characteristics and treatment information were available for 365 patients, 37.3% of whom had metastatic disease. Only 11.2% had a complete diagnostic workup for risk stratification. Among the nonmetastatic patients, 17.5% received curative-intent therapy, and 27.5% received no CDT. Among the metastatic patients, 59.6% received androgen deprivation therapy. The 3- and 5-year age-standardized relative survival for 491 patients with survival time information was 58.8% (95% confidence interval [CI], 48.5%-67.7%) and 56.9% (95% CI, 39.8%-70.9%), respectively. In a multivariable analysis, survival was considerably poorer among patients without CDT versus those with therapy.

Conclusions: This study shows that a large proportion of patients with PCa in SSA are not staged or are insufficiently staged and undertreated, and this results in unfavorable survival. These findings reemphasize the need for improving diagnostic workup and access to care in SSA in order to mitigate the heavy burden of the disease in the region.
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http://dx.doi.org/10.1002/cncr.33818DOI Listing
July 2021

Correction to: Patterns of glioblastoma treatment and survival over a 16-years period: pooled data from the German Cancer Registries.

J Cancer Res Clin Oncol 2021 Apr 13. Epub 2021 Apr 13.

Institute for Medical Epidemiology, Biometrics and Informatics (IMEBI), Interdisciplinary Center for Health Sciences, Medical School of the Martin-Luther-University Halle-Wittenberg, Magdeburger Str. 8, 06112, Halle (Saale), Germany.

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http://dx.doi.org/10.1007/s00432-021-03638-yDOI Listing
April 2021

Treatment effects of palliative care consultation and patient contentment: A monocentric observational study.

Medicine (Baltimore) 2021 Mar;100(12):e24320

Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinik und Poliklinik für Strahlentherapie.

Abstract: Palliative care is a central component of the therapy in terminally ill patients. During treatment in non-palliative departments this can be realized by consultation.To analyze the change in symptom burden during palliative care consultation.In this observational study, we enrolled all cancer cases (n = 163) receiving inpatient treatment for 2015 to 2018 at our institution. We used the MDASI-questionnaire (0 = 'not present' and 10 = "as bad as you can imagine") and the FAMCARE-6 (1 = very satisfied, 5 = very dissatisfied) to analyze the treatment effect and patient satisfaction, respectively.We examined the association of symptom burden and patient satisfaction using Spearman-correlation. Comparing mean values, we applied the Wilcoxon-test and one-way ANOVA.An improvement in MDASI-core-items after treatment completion was significant (P < .05) in 14/18 symptoms. The change in perception of pain showed the strongest improvement (median: 5 to 3). Initially the MDASI-items "activity" (median = 8) and emotional distress (median = 5 and 6) were viewed as especially incriminating. There was no evidence for a correlation between patients' age, the type of diagnosis and time since diagnosis.The analysis of FAMCARE-6 patient contentment was lower or equal to two in all of the six items. There was a weak negative association between the change in symptom burden of psycho-emotional items "distress/feeling upset" (P = .006, rSp = -0,226), "sadness" and patient satisfaction in FAMCARE-6.A considerable improvement of the extensive symptom burden particularly of pain relief was achieved by integrating palliative consultation in clinical practice.
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http://dx.doi.org/10.1097/MD.0000000000024320DOI Listing
March 2021

Patterns of glioblastoma treatment and survival over a 16-years period: pooled data from the German Cancer Registries.

J Cancer Res Clin Oncol 2021 Mar 20. Epub 2021 Mar 20.

Institute for Medical Epidemiology, Biometrics and Informatics (IMEBI), Interdisciplinary Center for Health Sciences, Medical School of the Martin-Luther-University Halle-Wittenberg, Magdeburger Str. 8, 06112, Halle (Saale), Germany.

Introduction: Glioblastoma multiforme (GBM) is a primary malignant brain tumour characterized by a very low long-term survival. The aim of this study was to analyse the distribution of treatment modalities and their effect on survival for GBM cases diagnosed in Germany between 1999 and 2014.

Methods: Cases were pooled from the German Cancer Registries with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes for GBM or giant-cell GBM. Three periods, first (January 1999-December 2005), second (January 2006-December 2010) and a third period (January 2011-December 2014) were defined. Kaplan-Meier plots with long-rank test compared median overall survival (OS) between groups. Survival differences were assessed with Cox proportional-hazards models adjusted for available confounders.

Results: In total, 40,138 adult GBM cases were analysed, with a mean age at diagnosis 64.0 ± 12.4 years. GBM was more common in men (57.3%). The median OS was 10.0 (95% CI 9.0-10.0) months. There was an increase in 2-year survival, from 16.6% in the first to 19.3% in the third period. When stratified by age group, period and treatment modalities, there was an improved median OS after 2005 due to treatment advancements. Younger age, female sex, surgical resection, use of radiotherapy and chemotherapy, were independent factors associated with better survival.

Conclusion: The inclusion of temozolomide chemotherapy has considerably improved median OS in the older age groups but had a lesser effect in the younger age group of cases. The analysis showed survival improvements for each treatment option over time.
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http://dx.doi.org/10.1007/s00432-021-03596-5DOI Listing
March 2021

Lung Cancer Attributed Mortality Among 316,336 Early Stage Breast Cancer Cases Treated by Radiotherapy and/or Chemotherapy, 2000-2015: Evidence From the SEER Database.

Front Oncol 2020 25;10:602397. Epub 2021 Feb 25.

Department of Radiation Oncology, Faculty of Medicine, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.

Objective: To estimate the risk of death from lung cancer in patients treated for breast cancer (BC) in relation to the general population.

Methods: BC data, covering 2000 to 2015, were extracted from the Surveillance, Epidemiology and End Results-18 (SEER-18) cancer registry database. A comparison of lung cancer attributed mortality between BC patients and the general population was performed using standardized mortality ratios (SMRs) and SMRs conditional on survival length (cSMRs). Prognostic factors of lung cancer mortality were identified using flexible parametric modelling. Our model adjusts the effect of downstream (histopathological BC tumor grade and hormone receptor status) and upstream (age at diagnosis, ethnicity, and marital status) factors.

Results: The median follow-up was 6.4 years (interquartile range, 3.0-10.3 years). BC cases who received only radiotherapy (cSMR = 0.93; 95%CI: 0.77-1.13), only chemotherapy (cSMR = 0.91; 0.62-1.33), and radio-and chemotherapy (cSMR = 1.04; 0.77-1.39) had no evidence of increased lung cancer mortality relative to the general population. The adjusted model identified that lung cancer mortality was higher for women who were older at diagnosis compared to those <50 years (ranging from HR50-59 = 3.41 [95%CI: 2.72-4.28] to HR70-79 = 10.53 [95%CI: 8.44-13.13]) and for cases with negative estrogen and progesterone receptors (HR =1.38; 95% CI: 1.21-1.57). Compared to married cases, widowed, divorced, single or others had a 76%, 45%, and 25% higher hazard of lung cancer mortality, respectively. Lung cancer mortality was lower for American Indian/Alaska Native and Asian/Pacific Islander ethnicities (HR = 0.51; 95% CI: 0.40-0.64) compared to BC cases with white ethnic background.

Conclusions: There is no evidence for a higher lung cancer mortality in BC patients when compared to the general population.
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http://dx.doi.org/10.3389/fonc.2020.602397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947230PMC
February 2021

Corrigendum: Early Mortality of Prostatectomy vs. Radiotherapy as a Primary Treatment for Prostate Cancer: A Population-Based Study From the United States and East Germany.

Front Oncol 2021 5;11:635433. Epub 2021 Feb 5.

Department of Radiation Oncology, University Hospital Halle (Saale), Halle (Saale), Germany.

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http://dx.doi.org/10.3389/fonc.2021.635433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894203PMC
February 2021

Socioeconomic disparities in head and neck cancer survival in Germany: a causal mediation analysis using population-based cancer registry data.

J Cancer Res Clin Oncol 2021 May 11;147(5):1325-1334. Epub 2021 Feb 11.

Department of Radiation Oncology, Health Services Research Group, University Hospital Halle (Saale), Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany.

Purpose: Despite recent improvements in cancer treatment in Germany, a marked difference in cancer survival based on socioeconomic factors persists. We aim to quantify the effect of socioeconomic inequality on head and neck cancer (HNC) survival.

Methods: Information on 20,821 HNC patients diagnosed in 2009-2013 was routinely collected by German population-based cancer registries. Socioeconomic inequality was defined by the German Index of Socioeconomic Deprivation. The Cox proportional regression and relative survival analysis measured the survival disparity according to level of socioeconomic deprivation with respective confidence intervals (CI). A causal mediation analysis was conducted to quantify the effect of socioeconomic deprivation mediated through medical care, stage at diagnosis, and treatment on HNC survival.

Results: The most socioeconomically deprived patients were found to have the highest hazard of dying when compared to the most affluent (Hazard Ratio: 1.25, 95% CI 1.17-1.34). The most deprived patients also had the worst 5-year age-adjusted relative survival (50.8%, 95% CI 48.5-53.0). Our mediation analysis showed that most of the effect of deprivation on survival was mediated through differential stage at diagnosis during the first 6 months after HNC diagnosis. As follow-up time increased, medical care, stage at diagnosis, and treatment played no role in mediating the effect of deprivation on survival.

Conclusion: This study confirms the survival disparity between affluent and deprived HNC patients in Germany. Considering data limitations, our results suggest that, within six months after HNC diagnosis, the elimination of differences in stage at diagnosis could reduce survival inequalities.
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http://dx.doi.org/10.1007/s00432-021-03537-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021523PMC
May 2021

Effect of Radiotherapy in Addition to Surgery in Early Stage Endometrial Cancer: A Population-Based Study.

Cancers (Basel) 2020 Dec 17;12(12). Epub 2020 Dec 17.

Department of Radiation Oncology, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany.

Background: The role of radiotherapy in the management of early (FIGO I) endometrial cancer is controversial with limited availability of prospective data from randomized trials.

Methods: German Epidemiologic Cancer Registries provided by the Robert Koch Institute. We considered FIGO I cases with recorded operative treatment ( = 12,718, 2000-2017). We computed hazard ratios (HR) from relative survival models in relation to the mortality of the general population with 95% confidence intervals (CI). Multivariate models were adjusted for age, stage (IA vs. IB), grading, and chemotherapy. Radiotherapy included external radiotherapy and brachytherapy.

Results: Cases with a favorable risk profile (FIGO IA, G1/G2) had a slightly lower survival rate, relative to the general population (FIGO IA: 0.9, G1: 0.91). The proportion of FIGO IA cases was lower in the radiotherapy group (52.6%) vs. cases without radiotherapy (78.6%). Additional treatment with radiotherapy was beneficial in FIGO IB (HR = 0.74) and all histopathological grades, but not FIGO IA cases (HR = 0.93) cases. Compared to IA tumors, IB cases had a HR of 1.51 (95% CI: 1.34-1.7).

Conclusions: Radiotherapy in addition to surgery is beneficial for patients in a FIGO IB stage. Further studies need to address the impact of new techniques and risk assessment.
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http://dx.doi.org/10.3390/cancers12123814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766752PMC
December 2020

The Role of Postoperative Radiotherapy for Carcinosarcoma of the Uterus.

Cancers (Basel) 2020 Nov 30;12(12). Epub 2020 Nov 30.

Department of Radiation Oncology, CyberKnife and Radiotherapy, Medical Faculty University Cologne, 50937 Cologne, Germany.

The role of postoperative radiotherapy delivered as external-beam radiotherapy (EBRT), vaginal brachytherapy (VBT) or a combination of both, in the management of carcinosarcoma of the uterus is not clearly defined, as only limited randomized trial data are available, indicating a reduction in locoregional recurrences after EBRT. We performed a structured review of data published from 2010. Although no relevant new data from prospective trials or meta-analyses were identified, 14 analyses of cancer registry data from the United States or Europe, focusing predominantly on the endpoint for overall survival, were identified, four of them using propensity-score matching to compare subgroups treated with vs. without radiotherapy. Although stage-by-stage data are rare, the registry analyses support the idea of a beneficial effect, especially of VBT, on overall survival in International Federation of Gynecology and Obstetrics (FIGO) stage IA patients (to a lesser extent in stage IB). For stages II to III, the data sets indicate the largest effects on overall survival for the combination of EBRT and VBT. In all stages, survival effects of radiotherapy apparently persist when given in addition to chemotherapy. Whereas some studies see the strongest survival effects in patients with positive lymph nodes, propensity-score matched data indicate an overall survival effect of radiotherapy (EBRT + VBT or VBT alone) in FIGO stages I to III regardless of lymph node surgery.
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http://dx.doi.org/10.3390/cancers12123573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760981PMC
November 2020

Do extreme summers increase blood vitamin D (25-hydroxyvitamin D) levels?

PLoS One 2020 10;15(11):e0242230. Epub 2020 Nov 10.

Central Laboratory, University Hospital Halle, Halle/Saale, Germany.

Climate change is expected to increase the frequency of extreme weather events, such as extended heat waves and droughts in the northern hemisphere. Besides affecting ecosystems worldwide, these changes in climate patterns will also affect the environmental health of human populations. While the medical community is mostly concerned with the negative impact of climate change, there might also be some beneficial effects. In this study we used laboratory data from a large university clinic in Germany (n = 13 406), to test for any detectable impact of two extreme summers on Vitamin-D [25(OH)D] plasma concentrations over a six year period (2014-2019). For the two years with extreme summers (2018 and 2019) the 25(OH)D plasma concentrations were significantly higher than in the previous four years (p < 0.001). A time series analysis (autoregressive term, AR, φ = 0.84, with an AR of one indicating a persistent effect) showed that 25(OH)D concentrations rise by 0.04 nmol/l (95% CI: 0.04-0.05 nmol/l) per hour of sunshine. The incidence of vitamin D deficiency was generally high (60% for 2014-2017) but dropped by 10% in 2018 and 2019. As such, the summers of 2018 and 2019, which are among the hottest and driest in Germany since the start of modern climate recordings, had a measurable positive effect on 25(OH)D plasma levels of the examined population. Given that 25(OH)D deficiency is widespread in higher latitudes, this implies that while mostly considered negative, climate change might also confer some health benefits with regard to vitamin D related medical conditions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242230PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654803PMC
December 2020

The association between change of soluble tumor necrosis factor receptor R1 (sTNF-R1) measurements and cardiovascular and all-cause mortality-Results from the population-based (Cardiovascular Disease, Living and Ageing in Halle) CARLA study 2002-2016.

PLoS One 2020 26;15(10):e0241213. Epub 2020 Oct 26.

Institute of Medical Epidemiology, Biometrics and Informatics, Interdisciplinary Center for Health Sciences, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Saxony-Anhalt, Germany.

Aims: Single measurements of higher levels of soluble tumor necrosis factor receptor I (sTNF-R1) have been shown to be associated with increased risk of mortality. However, up to date, little is known about the underlying temporal dynamics of sTNF-R1 concentrations and their relation with mortality. We aimed to characterize the effect of changes in sTNFR-1 levels on all-cause and cardiovascular mortality, independent from other established risk factors for mortality, including other inflammatory markers.

Methods: We used data of the population based cohort study CARLA and included 1408 subjects with sTNF-R1 measured at baseline (2002-2006) and first follow-up (2007-2010). Cox proportional hazard models were used to assess the association of baseline and follow-up sTNF-R1 measurements with all-cause and cardiovascular mortality during ~10 years since the first follow-up after adjusting for relevant confounders.

Results: Based on 211 deaths among 1408 subjects, per each doubling of the baseline sTNF-R1, the risk of all-cause mortality was increased by about 30% (Hazard ratio 1.28, 95% Confidence Interval 0.6-2.7), while per each doubling of the follow-up level of sTNF-R1 mortality was 3-fold (3.11, 1.5-6.5) higher in a model including both measurements and adjusting for confounders. The results were mainly related to the cardiovascular mortality (5.9, 2.1-16.8 per each doubling of follow up sTNF-R1 value).

Conclusion: Solely the follow-up value, rather than its change from baseline, predicted future mortality. Thus, while sTNF-R1 levels are associated with mortality, particularly cardiovascular, over a long-time period in the general population, if they change, the earlier measurements play no or little role.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241213PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588092PMC
December 2020

Association of familial history of diabetes or myocardial infarction and stroke with risk of cardiovascular diseases in four German cohorts.

Sci Rep 2020 09 21;10(1):15373. Epub 2020 Sep 21.

Department of Food Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, Berlin, Germany.

Since family history of diabetes is a very strong risk factor for type 2 diabetes, which is one of the most important risk factors for cardiovascular disease (CVD), it might be also useful to assess the risk for CVD. Therefore, we aimed to investigate the relationship between a familial (parents and siblings) history of diabetes and the risk of incident CVD. Data from four prospective German cohort studies were used: EPIC-Potsdam study (n = 26,054), CARLA study (n = 1,079), SHIP study (n = 3,974), and KORA study (n = 15,777). A multivariable-adjusted Cox regression was performed to estimate associations between familial histories of diabetes, myocardial infarction or stroke and the risk of CVD in each cohort; combined hazard ratios (HR) were derived by conducting a meta-analysis. The history of diabetes in first-degree relatives was not related to the development of CVD (HR 0.99; 95% CI 0.88-1.10). Results were similar for the single outcomes myocardial infarction (MI) (HR 1.07; 95% CI 0.92-1.23) and stroke (HR 1.00; 95% CI 0.86-1.16). In contrast, parental history of MI and stroke were associated with an increased CVD risk. Our study indicates that diabetes in the family might not be a relevant risk factor for the incidence of CVD. However, the study confirmed the relationship between a parental history of MI or stroke and the onset of CVD.
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http://dx.doi.org/10.1038/s41598-020-72361-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505832PMC
September 2020

Metabolically Healthy, but Obese Individuals and Associations with Echocardiographic Parameters and Inflammatory Biomarkers: Results from the CARLA Study.

Diabetes Metab Syndr Obes 2020 27;13:2653-2665. Epub 2020 Jul 27.

Institute of Medical Epidemiology, Biostatistics, and Informatics (IMEBI), Interdisciplinary Center for Health Sciences, Medical School of the Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.

Introduction: The research on heterogeneity among obese individuals has identified the metabolically healthy, but obese (MHO) phenotype as a distinct group that does not experience the typical cardiovascular-related diseases (CVD). It is unclear if this group differs with regard to preconditions for CVDs. Our aim was to assess differences in echocardiographic parameters and inflammatory biomarkers between MHO and metabolically healthy, normal weight individuals (MHNW).

Methods: The analyses used data from 1412 elderly participants from a German population-based cohort study (CARLA), which collected detailed information on demographic, biochemical, and echocardiographic variables. Participants were subdivided into four groups (MHNW, MHO, MUNW (metabolically unhealthy, normal weight) and MUO (metabolically unhealthy, obese)) based on BMI≥30 kg/m (obese or normal weight) and presence of components of the metabolic syndrome. The clinical characteristics of the 4 groups were compared with ANOVA or Chi-Square test, in addition to two linear regression models for 16 echocardiographic parameters. The difference in inflammatory biomarkers (hsCRP, IL-6 and sTNF-RI) between the groups was examined with a multinomial logistic regression model.

Results: The MHO individuals were on average 64.2±8.4 years old, with a higher proportion of women (71.6%), low percentage of smokers, larger waist circumference (109.3±10.5 cm vs 89.1±10.8 cm, p<0.0001) and higher odds ratios for hsCRP, IL-6 and sTNF-RI compared to MHNW individuals. Linear regression models revealed greater left atrial (LA) diameter (2.73 (95% CI: 1.35-4.11) mm), LA volume (7.86 (95% CI: 2.88-12.83) mL), and left ventricular mass index (LVMI) (11.82 (95% CI: 4.43-19.22) g/m) in the MHO group compared to the MHNW group.

Conclusion: The MHO phenotype is associated with echocardiographic markers of cardiac remodeling (LA diameter, volume and LVMI) and higher odds ratios for inflammatory biomarkers.
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http://dx.doi.org/10.2147/DMSO.S263727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419616PMC
July 2020

Predictors of the regional variation of prostatectomy or radiotherapy: evidence from German cancer registries.

J Cancer Res Clin Oncol 2020 May 4;146(5):1197-1204. Epub 2020 Mar 4.

Department for Radiation Oncology, Martin-Luther University Halle-Wittenberg, Halle, Germany.

Objective: To assess the association of public health parameters with the regional variation in the initial treatment for prostate cancer.

Methods: We used data from German epidemiologic cancer registries for the years 2009-2013. Presence of a certified cancer center, a radiotherapy and/or urology institution, the district-specific GDP, and population density were used as predictors. Patients with indication for adjuvant treatment were excluded (T3b). Only districts with defined quality criteria were eligible. We used general linear mixed models (equivalent to logistic regression) with a covariance matrix weighted by the Euclidean distances between districts. Models were adjusted for age, grading, and TNM stage. We performed sensitivity analyses by imputing missing data with multiple imputation and considering extreme case scenarios. We applied inverse probability weighting to account for missing values.

Results: When radiotherapy/surgery is compared to neither treatment, the probability for the latter was higher in East than in West Germany (OR 1.7, 95% CI 1.43-2.02). The same was true for districts with both, a radiotherapy and urologic treatment facility (OR 1.43, 1.19-1.72). Analyzing radiotherapy vs. surgery, the probability for prostatectomy was inversely associated with the presence of a radiotherapy unit when compared to districts with neither treatment facility (OR 0.52, 95% CI 0.38-0.73). Patients treated in East Germany were more likely to receive a surgical treatment (OR 1.34, 95% CI 1.08-1.66). Sensitivity analyses revealed no relevant change of effect estimates.

Conclusion: Treatment differs between East and West Germany and is associated with the presence of a radiotherapy or urology clinic.
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http://dx.doi.org/10.1007/s00432-020-03140-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142037PMC
May 2020

Benefit from surgery with additional radiotherapy in N1 head and neck cancer at the time of IMRT: A population-based study on recent developments.

PLoS One 2020 26;15(2):e0229266. Epub 2020 Feb 26.

Department of Radiation Oncology, Martin Luther University Halle-Wittenberg, Halle (Saale), Saxony-Anhalt, Germany.

Background: Currently, the role of adjuvant irradiation in head and neck cancer (HNC) patients with N1-lymph node status is not clarified.

Objectives: To assess the population-based effect of recent developments in radiotherapy such as intensity-modulated radiotherapy (IMRT) in relation to overall survival (OS) together with surgery in N1 HNC patients.

Materials And Methods: We used 9,318 HNC cases with pT1/2 N0/1 disease from German cancer registries. Time of diagnosis ranged from January 2000 to December 2014, which we divided into three periods: (low [LIA] vs intermediate [IA] vs high [HIA] IMRT availability period) based on usage of IMRT in Germany. For each period, we examined a possible association between treatment (surgery vs. surgery and radiotherapy) in terms of OS. Statistical analyses included Kaplan-Meier and multivariate Cox regression (models adjusted for HPV-related cancer site).

Results: Temporal analysis revealed increasing usage of IMRT in Germany. In patients with N1 tumours, a comparison of patients treated with and without radiotherapy during the HIA period showed a superiority of the combined treatment as opposed to surgery alone (HR 0.54, 95%CI: 0.35-0.85, p = 0.003). The survival analyses related to treatments in terms of period underlined the superiority of surgery plus radiotherapy between periods IA and HIA (p = 0.03).

Conclusion: The advent of IMRT, additional radiotherapy may present a survival advantage in patients with N1 HNC when combined with surgery.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229266PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043743PMC
May 2020

Early Mortality of Prostatectomy vs. Radiotherapy as a Primary Treatment for Prostate Cancer: A Population-Based Study From the United States and East Germany.

Front Oncol 2019 17;9:1451. Epub 2020 Jan 17.

Department of Radiation Oncology, University Hospital Halle (Saale), Halle (Saale), Germany.

To assess the extent of early mortality and its temporal course after prostatectomy and radiotherapy in the general population. Data from the Surveillance, Epidemiology, and End Results (SEER) database and East German epidemiologic cancer registries were used for the years 2005-2013. Metastasized cases were excluded. Analyzing overall mortality, year-specific Cox regression models were used after adjusting for age (including age squared), risk stage, and grading. To estimate temporal hazards, we computed year-specific conditional hazards for surgery and radiotherapy after propensity-score matching and applied piecewise proportional hazard models. In German and US populations, we observed higher initial 3-month mortality odds for prostatectomy (USA: 9.4, 95% CI: 7.8-11.2; Germany: 9.1, 95% CI: 5.1-16.2) approaching the null effect value not before 24-months (estimated annual mean 36-months in US data) after diagnosis. During the observational period, we observed a constant hazard ratio for the 24-month mortality in the US population (2005: 1.7, 95% CI: 1.5-1.9; 2013: 1.9, 95% CI: 1.6-2.2) comparing surgery and radiotherapy. The same was true in the German cohort (2005: 1.4, 95% CI: 0.9-2.1; 2013: 3.3, 95% CI: 2.2-5.1). Considering low-risk cases, the adverse surgery effect appeared stronger. There is strong evidence from two independent populations of a considerably higher early to midterm mortality after prostatectomy compared to radiotherapy extending the time of early mortality considered by previous studies up to 36-months.
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http://dx.doi.org/10.3389/fonc.2019.01451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978671PMC
January 2020

One simple claudication question as first step in Peripheral Arterial Disease (PAD) screening: A meta-analysis of the association with reduced Ankle Brachial Index (ABI) in 27,945 subjects.

PLoS One 2019 4;14(11):e0224608. Epub 2019 Nov 4.

DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.

Purpose And Methods: A meta-analysis using data from seven German population-based cohorts was performed by the German Epidemiological consortium of Peripheral Arterial Disease (GEPArD) to investigate whether one question about claudication is more efficient for PAD screening than established questionnaires. Claudication was defined on the basis of the answer to one question asking for pain in the leg during normal walking. This simple question was compared with established questionnaires, including the Edinburgh questionnaire. The associations of claudication with continuous ABI values and decreased ABI were analyzed by linear and logistic regression analysis, respectively. The results of the studies were pooled in a random effect meta-analysis, which included data from 27,945 individuals (14,052 women, age range 20-84 years).

Results: Meta-analysis revealed a significant negative association between claudication and ABI, which was stronger in men (β = -0.07; 95%CI -0.10, -0.04) than in women (β = -0.02; 95%CI -0.02, -0.01). Likewise, the presence of claudication symptoms was related to an increased odds of a decreased ABI in both men (Odds ratio = 5.40; 95%CI 4.20, 6.96) and women (Odds ratio = 1.99; 95%CI 1.58, 2.51).

Conclusions: Asking only one question about claudication was able to identify many individuals with a high likelihood of a reduced ABI with markedly higher sensitivity and only slightly reduced specificity compared to more complex questionnaires. At least in men, this question should be established as first screening step.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224608PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827909PMC
April 2020

Mortality after radiotherapy or surgery in the treatment of early stage non-small-cell lung cancer: a population-based study on recent developments.

J Cancer Res Clin Oncol 2019 Nov 6;145(11):2813-2822. Epub 2019 Sep 6.

Department of Radiation Oncology, Martin Luther University, Halle, Germany.

Background: Stereotactic body radiotherapy (SBRT) can achieve high tumour control with limited toxicity for inoperable early stage non-small-cell lung cancer (NSCLC) patients.

Patients And Methods: The German Epidemiologic Cancer Registries from the Robert-Koch Institute were assessed. Periods according to the availability of SBRT were: (1) 2000-2003 (pre-SBRT); (2) 2004-2007 (interim); and (3) 2007-2014 (broad availability of SBRT). To assess the association of cancer-related parameters with mortality, hazard ratios (HR) from Cox proportional hazards models were computed. To evaluate the change of treatment-related mortality, we performed interaction analyses and the relative excess risk due to interaction (RERI, additive scale) was computed.

Results: A total of 16,292 patients with UICC stage I NSCLC diagnosed between 2000 and 2014 were analysed. Radiotherapy utilization increased from 5% in pre-SBRT era to 8.8% after 2007. In univariate analyses, survival in the whole cohort improved only marginally when 2000-2003 is compared to 2004-2007 (HR 0.92, 95% CI 0.85-1.01) or 2008-2014 (HR 0.93, 95% CI 0.86-1.01). Comparing surgery/radiotherapy, mortality in the radiotherapy group started from a 3.5-fold risk in 2000-2003 to 2.6 after 2007. The interaction analysis revealed a stronger improvement for radiotherapy (multiplicative scale for 2000-2003 vs. > 2007: 0.74, 95% CI 0.58-0.94). On an additive scale, treatment × period interaction revealed an RERI for 2000-2003 vs. > 2007 of - 1.18 (95% CI - 1.8, - 0.55).

Conclusions: Using population-based data, we observed a survival improvement in stage I lung cancer over time. With an increasing utilization of radiotherapy, a stronger improvement occurred in patients treated with radiotherapy when compared to surgery.
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http://dx.doi.org/10.1007/s00432-019-03013-yDOI Listing
November 2019

Association of domain-specific physical activity and cardiorespiratory fitness with all-cause and cause-specific mortality in two population-based cohort studies.

Sci Rep 2018 10 30;8(1):16066. Epub 2018 Oct 30.

Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.

Physical activity (PA) reduces the risk for mortality. Whether the beneficial effects of PA are domain specific is unclear. We associated leisure time (LTPA), sports (SPA) and work (WPA) related PA and cardiorespiratory fitness (CRF) with all-cause mortality in two German population-based cohorts. We used data of the Study of Health in Pomerania (SHIP, n = 2,935, median age 53; 48% male) and the Cardiovascular Disease, Living and Ageing in Halle study (CARLA, n = 1,776, median age 64 and 54% male). Mortality was determined after a median follow-up of 8.2 years in SHIP (n = 332) and 11.5 years in CARLA (n = 409). LTPA (SHIP: hazard ratio [HR] per standard deviation [SD] 0.82 95%-CI 0.73 to 0.91 and CARLA: HR per SD 0.70: 95%-CI 0.59 to 0.82) and SPA (SHIP: HR per SD 0.80 95%-CI 0.71 to 0.91 and CARLA: HR per SD 0.70 95%-CI 0.60 to 0.82) but not WPA were inversely associated with all-cause mortality. In a subsample CRF was inversely related to mortality and positively to LTPA and sports SPA. No association was found for WPA. Our results may suggest that the inverse association between PA and mortality are partly influenced by higher CRF.
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http://dx.doi.org/10.1038/s41598-018-34468-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207740PMC
October 2018

Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

Nat Commun 2018 10 26;9(1):4455. Epub 2018 Oct 26.

Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets.
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http://dx.doi.org/10.1038/s41467-018-06356-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203810PMC
October 2018

Number of radiotherapy treatment machines in the population and cancer mortality: an ecological study.

Clin Epidemiol 2018 21;10:1249-1273. Epub 2018 Sep 21.

Department of Radiation Oncology, University Hospital Halle (Saale), Halle (Saale), Germany,

Objectives: The aim of this study was to assess the association between the number of radiotherapy treatment machines (RTMs) in the population and incidence-adjusted cancer mortality.

Methods: Data on cancer incidence and mortality were obtained from the GLOBOCAN project (only high-quality data, C3, or higher according to GLOBOCAN quality label), information on the number of RTMs from the Directory of Radiotherapy Centers database, and remaining data from the World Bank and World Health Organization database. We used linear regression models to assess the associations between RTM per 10,000,000 inhabitants (logarithmized) and the log-transformed mortality/incidence ratio. Models were adjusted for public health variables. To assess the bias due to unobserved confounders, mortality from leukemia was considered as a negative control. Here radiotherapy treatment is less frequently applied, but a common set of confounders is shared with cancer types where radiotherapy plays a stronger role, enabling us to estimate the bias due to confounding of unmeasured parameters. To assess an exposure-effect size relationship, estimated cancer type-specific estimates were related to the proportion of subjects receiving radiotherapy.

Results: We found an inverse linear relationship between RTM in the population and the cancer mortality to incidence ratio for prostate cancer (14.1% per doubling of RTM; 95% CI: 0.1%-26.1%), female breast cancer (12.3%; 95% CI: 2.7%-20.9%), and lung cancer in women (11.2%; 95% CI: 4.3%-17.6%). There was no evidence for bias due to unobserved confounders after covariate adjustment. For women, an exposure-effect size relationship was found (=0.02).

Conclusion: In this ecological study, we found evidence that the population density of RTM is related to cancer mortality independently of other public health parameters.
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http://dx.doi.org/10.2147/CLEP.S156764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163015PMC
September 2018

Health services research in German radiation oncology: new opportunities to advance cancer care.

Strahlenther Onkol 2018 Dec 4;194(12):1097-1102. Epub 2018 Sep 4.

Department of Radiation Oncology, University Hospital Halle (Saale), Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany.

Background: Health services research (HSR) is of increasing relevance to scientists, health-care providers, and clinicians. Complex population-based secondary data are a key source of information for analyses of health-care effects in radiation oncology.

Methods: In this short paper, we examine potential applications of secondary data focusing on statistics from the diagnosis-related groups (DRG). This data set incorporating all hospitalized cases in Germany is based on claims of reimbursements and is provided by the Research Data Centers (RDC) of the Federal Statistical Office and the Statistical Offices of the federal states. A short outlook regarding other data sources is also presented.

Results: In radiation oncology, secondary data such as the DRG statistics have rarely been used to examine health-care effects, despite their great potential for reporting effects in a broad population-based setting. Furthermore, for most data sources, the application to use these data is accessible with minor effort. However, data concerning outpatient care are difficult to analyze on a comparable level.

Conclusion: DRG statistics and related secondary data provide a remarkable source of information for analyses of health-care-related effects in radiation oncology.
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http://dx.doi.org/10.1007/s00066-018-1357-4DOI Listing
December 2018

Predictive and prognostic value of tumor volume and its changes during radical radiotherapy of stage III non-small cell lung cancer : A systematic review.

Strahlenther Onkol 2018 02 13;194(2):79-90. Epub 2017 Oct 13.

Department of Radiation Oncology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany.

Purpose: Lung cancer remains the leading cause of cancer-related mortality worldwide. Stage III non-small cell lung cancer (NSCLC) includes heterogeneous presentation of the disease including lymph node involvement and large tumour volumes with infiltration of the mediastinum, heart or spine. In the treatment of stage III NSCLC an interdisciplinary approach including radiotherapy is considered standard of care with acceptable toxicity and improved clinical outcome concerning local control. Furthermore, gross tumour volume (GTV) changes during definitive radiotherapy would allow for adaptive replanning which offers normal tissue sparing and dose escalation.

Methods: A literature review was conducted to describe the predictive value of GTV changes during definitive radiotherapy especially focussing on overall survival. The literature search was conducted in a two-step review process using PubMed®/Medline® with the key words "stage III non-small cell lung cancer" and "radiotherapy" and "tumour volume" and "prognostic factors".

Results: After final consideration 17, 14 and 9 studies with a total of 2516, 784 and 639 patients on predictive impact of GTV, GTV changes and its impact on overall survival, respectively, for definitive radiotherapy for stage III NSCLC were included in this review. Initial GTV is an important prognostic factor for overall survival in several studies, but the time of evaluation and the value of histology need to be further investigated. GTV changes during RT differ widely, optimal timing for re-evaluation of GTV and their predictive value for prognosis needs to be clarified. The prognostic value of GTV changes is unclear due to varying study qualities, re-evaluation time and conflicting results.

Conclusion: The main findings were that the clinical impact of GTV changes during definitive radiotherapy is still unclear due to heterogeneous study designs with varying quality. Several potential confounding variables were found and need to be considered for future studies to evaluate GTV changes during definitive radiotherapy with respect to treatment outcome.
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http://dx.doi.org/10.1007/s00066-017-1221-yDOI Listing
February 2018

Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function.

J Clin Invest 2017 May 10;127(5):1798-1812. Epub 2017 Apr 10.

Background: Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function.

Methods: A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function.

Results: The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue.

Conclusion: The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies.

Funding: For detailed information per study, see Acknowledgments.
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http://dx.doi.org/10.1172/JCI84840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409098PMC
May 2017

Longitudinal association of short-term, metronome-paced heart rate variability and echocardiographically assessed cardiac structure at a 4-year follow-up: results from the prospective, population-based CARLA cohort.

Europace 2017 Dec;19(12):2027-2035

Institute of Medical Epidemiology, Biostatistics and Informatics, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany.

Aims: To assess the value of cardiac structure/function in predicting heart rate variability (HRV) and the possibly predictive value of HRV on cardiac parameters.

Methods And Results: Baseline and 4-year follow-up data from the population-based CARLA cohort were used (790 men, 646 women, aged 45-83 years at baseline and 50-87 years at follow-up). Echocardiographic and HRV recordings were performed at baseline and at follow-up. Linear regression models with a quadratic term were used. Crude and covariate adjusted estimates were calculated. Missing values were imputed by means of multiple imputation. Heart rate variability measures taken into account consisted of linear time and frequency domain [standard deviation of normal-to-normal intervals (SDNN), high-frequency power (HF), low-frequency power (LF), LF/HF ratio] and non-linear measures [detrended fluctuation analysis (DFA1), SD1, SD2, SD1/SD2 ratio]. Echocardiographic parameters considered were ventricular mass index, diastolic interventricular septum thickness, left ventricular diastolic dimension, left atrial dimension systolic (LADS), and ejection fraction (Teichholz). A negative quadratic relation between baseline LADS and change in SDNN and HF was observed. The maximum HF and SDNN change (an increase of roughly 0.02%) was predicted at LADS of 3.72 and 3.57 cm, respectively, while the majority of subjects experienced a decrease in HRV. There was no association between further echocardiographic parameters and change in HRV, and there was no evidence of a predictive value of HRV in the prediction of changes in cardiac structure.

Conclusion: In the general population, LADS predicts 4-year alteration in SDNN and HF non-linearly. Because of the novelty of the result, analyses should be replicated in other populations.
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http://dx.doi.org/10.1093/europace/euw296DOI Listing
December 2017

Cancer mortality in former East and West Germany: a story of unification?

BMC Cancer 2017 02 2;17(1):94. Epub 2017 Feb 2.

Department of Radiation Oncology, University Hospital Halle (Saale), Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany.

Background: Health and social conditions vary between West and East Germany.

Methods: We analyzed annual mortality data of all recorded deaths caused by lung, colorectal, breast and prostate cancer in Germany as they are published by the Federal Bureau of Statistics (FBS) encompassing the period 1980-2014 for former West Germany (WG) and 1990-2014 for former East Germany (EG). To compare East and West Germany we computed the ratio of the mortality rates in both parts (mortality rate ratio, MRR, <1 indicates a lower mortality in EG). Forecasting methods of time series analyses were applied (model selection based on the Box/Jenkins approach) to predict 5-year trends until 2019.

Results: Lung cancer: In women mortality rose in both regions (WG: +2.8%, 1991-2014, EG: +2.2%, 1990-2014). In men mortality in WG declined between -2.1% and -1.2%, and by -2.7% (1993-2009) in EG which was followed by a plateau. Colorectal cancer: A decline was found in both WG (-3.1%, 1993-2014) and EG women (-3.8%, 1993-2008 and -2.0%, 2008-2014). A decline in EG men since 1992 (-0.9%, 1992-1997 and -2.3%, 1997-2014) mirrors the development in WG (-2.6%, 1995-2014). Breast cancer: Constant mortality decline in WG after 1996. In EG a decline (-2.4%, 1992-2007) was followed by a plateau with an MRR <1 (1990-2014). Prostate cancer: In WG a decline (-3.4%) came to a hold after 2007, while there was a constant decline of 1.5% in EG. The forecast indicated that mortality of colorectal/lung cancer in men and breast cancer reaches a plateau in future years.

Conclusion: Courses of mortality were similar between East and West, while existing differences are likely to remain in the near future.
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http://dx.doi.org/10.1186/s12885-017-3086-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288858PMC
February 2017

Short-term blood pressure variability - variation between arm side, body position and successive measurements: a population-based cohort study.

BMC Cardiovasc Disord 2017 01 18;17(1):31. Epub 2017 Jan 18.

Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther University Halle-Wittenberg, Magdeburger Str. 8, 06112, Halle Saale, Germany.

Background: Precise blood pressure (BP) measurements are central for the diagnosis of hypertension in clinical and epidemiological studies. The purpose of this study was to quantify the variability in BP associated with arm side, body position, and successive measurements in the setting of a population-based observational study. Additionally, we aimed to evaluate the influence of different measurement conditions on prevalence of hypertension.

Methods: The sample included 967 men and 812 women aged 45 to 83 years at baseline. BP was measured according to a standardized protocol with oscillometric devices including three sitting measurements at left arm, one simultaneous supine measurement at both arms, and four supine measurements at the arm with the higher BP. Hypertension was defined as systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg. Variability in SBP and DBP were analysed with sex-stratified linear covariance pattern models.

Results: We found that overall, no mean BP differences were measured according to arm-side, but substantial higher DBP and for men also higher SBP was observed in sitting than in supine position and there was a clear BP decline by consecutive measurement. Accordingly, the prevalence of hypertension depends strongly on the number and scheme of BP measurements taken to calculate the index values.

Conclusions: Thus, BP measurements should only be compared between studies applying equal measurement conditions and index calculation. Moreover, the first BP measurement should not be used to define hypertension since it overestimates BP. The mean of second and third measurement offers the advantage of better reproducibility over single measurements.
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http://dx.doi.org/10.1186/s12872-017-0468-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241970PMC
January 2017

Cardiovascular Risk Factors Associated With Blood Metabolite Concentrations and Their Alterations During a 4-Year Period in a Population-Based Cohort.

Circ Cardiovasc Genet 2016 Dec 26;9(6):487-494. Epub 2016 Oct 26.

From the Institute of Medical Epidemiology, Biostatistics and Informatics (M.E.L., A.K., D.T., D.M., J.H.), Clinic of Psychiatry, Psychotherapy, and Psychosomatics (I.G., D.R.), and Department of Medicine III, Martin-Luther University Halle-Wittenberg, Halle Saale, Germany (S.F.); Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (C.P., J.A.); Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany (J.A.); German Center for Diabetes Research (DZD), Neuherberg (J.A.); Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg (K.H.G.); Laboratory of Immunology, Wadsworth Center, New York State Department of Health, Albany (R.T.E.); and Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg (G.K.).

Background: The effects of lifestyle risk factors considered collectively on the human metabolism are to date unknown. We aim to investigate the association of these risk factors with metabolites and their changes during 4 years.

Methods And Results: One hundred and sixty-three metabolites were measured in serum samples with the AbsoluteIDQ kit p150 (Biocrates) following a targeted metabolomics approach, in a population-based cohort of 1030 individuals, aged 45 to 83 years at baseline. We evaluated associations between metabolite concentrations (28 acylcarnitines, 14 amino acids, 9 lysophosphocholines, 72 phosphocholines, 10 sphingomyelins and sum of hexoses) and 5 lifestyle risk factors (body mass index [BMI], alcohol consumption, smoking, diet, and exercise). Multilevel or simple linear regression modeling adjusted for relevant covariates was used for the evaluation of cross-sectional or longitudinal associations, respectively; multiple testing correction was based on false discovery rate. BMI, alcohol consumption, and smoking were associated with lipid metabolism (reduced lyso- and acyl-alkyl-phosphatidylcholines and increased diacylphosphatidylcholines concentrations). Smoking showed positive associations with acylcarnitines, and BMI correlated inversely with nonessential amino acids. Fewer metabolites showed relative changes that were associated with baseline risk factors: increases in 5 different acyl-alkyl phosphatidylcholines were associated with lower alcohol consumption and BMI and with a healthier diet. Increased levels of tyrosine were associated with BMI. Sex-specific effects of smoking and BMI were found specifically related to acylcarnitine metabolism: in women higher BMI and in men more pack-years were associated with increases in acylcarnitines.

Conclusions: This study showed sex-specific effects of lifestyle risks factors on human metabolism and highlighted their long-term metabolic consequences.
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http://dx.doi.org/10.1161/CIRCGENETICS.116.001444DOI Listing
December 2016
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