Institute for Biometry and Epidemiology

Düsseldorf, Germany

Institute for Biometry and Epidemiology

Düsseldorf, Germany
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Vijayakumar P.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases | Hoyer A.,Institute for Biometry and Epidemiology | Nelson R.G.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases | Brinks R.,Institute for Biometry and Epidemiology | Pavkov M.E.,Centers for Disease Control and Prevention
PLoS ONE | Year: 2017

The objective was to estimate chronic kidney disease (CKD) incidence rates from prevalence and mortality data, and compare the estimates with observed (true) incidence rates in a well-characterized population with diabetes. Pima Indians aged 20 years and older with type 2 diabetes were followed from 1982 through 2007. CKD was defined by estimated GFR (eGFR) <60 ml/min/1.72 m2 or albumin-to-creatinine ratio (ACR) ≥30 mg/g. True CKD incidence and mortality rates were computed for the whole study period, and prevalence for the intervals 1982-1994 and 1995-2007. Estimated age-sex stratified CKD incidence rates were computed using illness-death models of the observed prevalences, and of the wholeperiod mortality rate ratio of CKD to non-CKD persons. Among 1201 participants, 616 incident events of CKD occurred during a median follow-up of 5.6 years. Observed CKD prevalence was 56.9% (95%CI 53.7-60.0) and 48.0% (95%CI 45.2-50.8) in women; 54.0% (95% CI 49.9-58.1) and 49.6% (95%CI 46.0-53.3) in men, across the two periods. Mortality rate was 2.5 (95%CI 1.9-3.3) times as high in women with CKD and 1.6 (95%CI 1.3-2.1) times as high in men with CKD, compared to women or men without CKD. In women, estimated CKD incidence increased linearly from 25.6 (95%CI 4.2-53.0) to 128.6 (95%CI 77.1-196.6) with each 5-year age group up to 69 years, and to 99.8 (95%CI 38.7-204.7) at age ≥70. In men, estimated CKD incidence increased form 28.5 (95%CI 3.8-71.2) at age 20-24 years to 118.7 (95%CI 23.6-336.7) at age ≥70. Age-sex-stratified estimated incidence reflected the magnitude and directional trend of the true incidence and were similar to the true incidence rates (p>0.05 for difference) except for age 20-24 in women (p = 0.008) and age 25-29 in men (p = 0.002). In conclusion, the estimated and observed incidence rates of CKD agree well over 25 years of observation in this well characterized population with type 2 diabetes.

Brinks R.,Institute for Biometry and Epidemiology | Landwehr S.,Institute for Biometry and Epidemiology | Icks A.,Institute for Biometry and Epidemiology | Koch M.,Center for Nephrology | Giani G.,Institute for Biometry and Epidemiology
Statistics in Medicine | Year: 2013

This article describes new relationships between the age-specific incidence of, the prevalence of and mortality from a chronic disease. We express these relationships in terms of an ordinary differential equation and form the methodological basis for a novel approach to estimating incidences from age-specific prevalence data. We examine practical aspects of the relationships and a comparison with a known stochastic method in a simulation study. Finally, we apply the novel method to a data set of renal replacement therapy recorded from patients with chronic kidney failure in a region of Germany with approximately 310,000 inhabitants from 2002 to 2010. © 2012 John Wiley & Sons, Ltd.

Simon M.C.,Heinrich Heine University Düsseldorf | Bilan S.,Heinrich Heine University Düsseldorf | Nowotny B.,Heinrich Heine University Düsseldorf | Dickhaus T.,Humboldt University of Berlin | And 3 more authors.
Clinical and Experimental Immunology | Year: 2013

Summary: Fatty acids, uric acid and glucose are thought to contribute to subclinical inflammation associated with diabetes mellitus. We tested whether co-incubation of free fatty acids and uric acid or glucose influences the secretion of immune mediators from stimulated human whole blood in vitro. Fresh whole blood samples from 20 healthy subjects, 20 patients with type 1 diabetes and 23 patients with type 2 diabetes were incubated for 24h with palmitic acid (PAL), linolenic acid (LIN) or eicosapentaenoic acid (EPA) alone or together with elevated concentrations of uric acid or glucose. Concentrations of proinflammatory cytokines interleukin (IL)-1β, IL-2, IL-12(p70), IL-18, IFN-γ, of regulatory cytokines IL-4, IL-10, IL-17 and chemokine CCL2 (MCP-1) were measured by multiplex-bead technology from supernatants. Co-incubation of fatty acids with uric acid resulted in a significant reduction of IL-10, IL-12(p70), IFN-γ and CCL2 (MCP-1) concentrations in supernatants compared to incubation with uric acid alone (P<0·0001). In contrast, IL-18 was up-regulated upon co-stimulation with fatty acids and uric acid. Similarly, co-incubation of fatty acids with glucose diminished secretion of IL-10, IFN-γ and CCL2 (monocyte chemotactic protein-1), while IL-8 was up-regulated (P<0·001). Samples from healthy and diabetic subjects did not differ after adjustment for age, sex, body mass index and diabetes type. All three fatty acids similarly influenced whole blood cytokine release in vitro and modulated uric acid or glucose-stimulated cytokine secretion. Although the ω-3-fatty acid EPA showed slightly stronger effects, further studies are required to elaborate the differential effects of PAL, LIN and EPA on disease risk observed previously in epidemiological studies. Journal Compilation © 2013 British Society for Immunology.

Brinks R.,Institute for Biometry and Epidemiology | Brinks R.,Heinrich Heine University Düsseldorf | Hoyer A.,Institute for Biometry and Epidemiology | Landwehr S.,Heinrich Heine University Düsseldorf
PLoS ONE | Year: 2016

We propose two new methods to estimate secular trends in the incidence of a chronic disease from a series of prevalence studies and mortality data. One method is a direct inversion formula, the second method is a least squares estimation. Both methods are validated in a simulation study based on data from a diabetes register. The results of the validation show that the proposed methods may be useful in epidemiological settings with sparse resources, where running a register or a series of follow-up studies is difficult or impossible. © 2016 Brinks et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Laufs A.,Heinrich Group | Livingstone R.,Heinrich Group | Nowotny B.,Heinrich Group | Nowotny P.,Heinrich Group | And 6 more authors.
Magnetic Resonance in Medicine | Year: 2014

Purpose The aims of this study were (i) to establish a robust and fast method to quantify hepatocellular phosphorus compounds in molar concentration on a 3T clinical scanner, (ii) to evaluate its reproducibility, and (iii) to test its feasibility for a use in large cohort studies. Method Proton-decoupled 31P magnetic resonance spectroscopy of liver 31P compounds were acquired on 85 healthy subjects employing image selected in-vivo spectroscopy localization in 13 min of acquisition at 3T. Absolute quantification was achieved using an external reference and double-matching phantoms (inorganic phosphates and adenosine triphosphate (ATP) solutions). Reproducibility of the method was also examined. Results This method showed a high intra- and interday as well as inter- and intraobserver reproducibility (r > 0.98; P < 0.001), with a high signal to noise ratio (SNR) (i.e., mean SNR of γ-ATP: 16). The mean liver concentrations of 85 healthy subjects were assessed to be 1.99 ± 0.51 and 2.74 ± 0.55 mmol/l of wet tissue volume for Pi and γ-ATP, respectively. Conclusion This method reliably quantified molar concentrations of liver 31P compounds on 85 subjects with a short total examination time (25 min) on a 3T clinical scanner. Thus, the current method can be readily utilized for a clinical study, such as a large cohort study. © 2013 Wiley Periodicals, Inc.

Brinks R.,Institute for Biometry and Epidemiology | Landwehr S.,Institute for Biometry and Epidemiology | Waldeyer R.,Institute for Biometry and Epidemiology | Waldeyer R.,Heinrich Heine University Düsseldorf
Population Health Metrics | Year: 2013

Background: Age of onset is an important outcome to characterize a population with a chronic disease. With respect to social, cognitive, and physical aspects for patients and families, dementia is especially burdensome. In Germany, like in many other countries, it is highly prevalent in the older population and imposes enormous efforts for caregivers and society. Methods: We develop an incidence-prevalence-mortality model to derive the mean and variance of the age of onset in chronic diseases. Age- and sex-specific incidence and prevalence of dementia is taken from published values based on health insurance data from 2002. Data about the age distribution in Germany in 2002 comes from the Federal Statistical Office. Results: Mean age of onset of a chronic disease depends on a) the age-specific incidence of the disease, b) the prevalence of the disease, and c) the age distribution of the population. The resulting age of onset of dementia in Germany in 2002 is 78.8 ± 8.1 years (mean ± standard deviation) for men and 81.9 ± 7.6 years for women. Conclusions: Although incidence and prevalence of dementia in men are not greater than in women, men contract dementia approximately three years earlier than women. The reason lies in the different age distributions of the male and the female population in Germany. © 2013 Brinks et al.; licensee BioMed Central Ltd.

Brinks R.,Institute for Biometry and Epidemiology | Landwehr S.,Institute for Biometry and Epidemiology | Landwehr S.,Heinrich Heine University Düsseldorf
PLoS ONE | Year: 2015

A common modelling approach in public health and epidemiology divides the population under study into compartments containing persons that share the same status. Here we consider a three-state model with the compartments: A, B and Dead. States A and B may be the states of any dichotomous variable, for example, Healthy and Ill, respectively. The transitions between the states are described by change rates, which depend on calendar time and on age. So far, a rigorous mathematical calculation of the prevalence of property B has been difficult, which has limited the use of the model in epidemiology and public health. We develop a partial differential equation (PDE) that simplifies the use of the three-state model. To demonstrate the validity of the PDE, it is applied to two simulation studies, one about a hypothetical chronic disease and one about dementia in Germany. In two further applications, the PDE may provide insights into smoking behaviour of males in Germany and the knowledge about the ovulatory cycle in Egyptian women. © 2015 Brinks, Landwehr.

PubMed | Heinrich Heine University Düsseldorf, Institute for Biometry and Epidemiology and River Rhein Center For Rheumatology At St Elisabeth Hospital
Type: | Journal: Arthritis research & therapy | Year: 2016

Inhomogeneity of immune cell distribution in the synovial sublining layer was analyzed in order to improve our mechanistic understanding of synovial inflammation and explore potential refinements for histological biomarkers in rheumatoid arthritis (RA) and osteoarthritis (OA).Synovial tissue of 20 patients (11 RA, 9 OA) was immunohistochemically stained for macrophages (CD68), synovial fibroblasts (CD55), T cells (CD3), plasma cells (CD38), endothelial cells (vWF) and mast cells (MCT). The synovial sublining layer was divided into predefined adjacent zones and fractions of the stained area (SA) were determined by digital image analysis for each cell marker.Distribution of CD68, CD55, CD38 and MCT staining of the sublining area was heterogeneous (Friedman ANOVA p<0.05). The highest expression for all markers was observed in the upper layer close to the lining layer with a decrease in the middle and lower sublining. The SA of CD68, CD55 and CD38 was significantly higher in all layers of RA tissue compared to OA (p<0.05), except the CD38 fraction of the lower sublining. Based on receiver operating characteristics analysis, CD68 SA of the total sublining resulted in the highest area under the curve (AUC 0.944, CI 95% 0.844-1.0, p=0.001) followed by CD68 in the upper and middle layer respectively (both AUC 0.933, CI 95% 0.816-1.0, p=0.001) in both RA and OA. Linear mixed modelling confirmed significant differences in the SA of sublining CD68 between OA and RA (p=0.0042) with a higher concentration of CD68+ towards the lining layer and more rapid decline towards the periphery of the sublining in RA compared to OA (p=0.0022).Immune cells are inhomogeneously distributed within the sublining layer. RA and OA tissue display differences in the number of CD68 macrophages and differences in CD68 decline within the synovial sublining.

Brinks R.,Institute for Biometry and Epidemiology | Landwehr S.,Institute for Biometry and Epidemiology
Mathematical Medicine and Biology | Year: 2015

In 1991 Keiding published a relation between the age-specific prevalence and incidence of a chronic disease (in Age-specific incidence and prevalence: a statistical perspective. J. Roy. Stat. Soc. A, 154, 371-412). For special cases alternative formulations by differential equations were given recently in Brinks et al. (2013, Deriving age-specific incidence from prevalence with an ordinary differential equation. Statist. Med., 32, 2070-2078) and in Brinks and Landwehr (2014, Age- and time-dependent model of the prevalence of non-communicable diseases and application to dementia in Germany, Theor. Popul. Biol., 92, 62-68). From these works, we generalize formulations and discuss the advantages of the novel approach. As an implication, we obtain a new way of estimating the incidence rate of a chronic disease from prevalence data. This enables us to employ cross-sectional studies where otherwise expensive and lengthy follow-up studies are needed. © The authors 2014.

Brinks R.,Institute for Biometry and Epidemiology | Landwehr S.,Institute for Biometry and Epidemiology
Theoretical Population Biology | Year: 2014

We derive a partial differential equation (PDE) that models the age-specific prevalence of a disease as a function of the incidence, remission and mortality rates. The main focus is on non-communicable diseases (NCDs), although the PDE is not restricted to NCDs. As an application of the PDE, the number of persons with dementia in Germany until the year 2050 is estimated based on German incidence data and official population projections. Uncertainty is treated by different scenarios about life expectancy, number of migrants, prevalence of the disease in migrants, and scenarios about the future incidence, and mortality of demented persons. Life expectancy and incidence of dementia have the strongest impact on the future number of persons with dementia. In nearly all scenarios, our estimated case numbers exceed former estimates. Furthermore, we use an example to show that the PDE method yields more accurate results than a common alternative approach. © 2013 Elsevier Inc.

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