Population-Based Analysis of the Impact of Demographics on the Current and Future Blood Supply in the Saarland.

BACKGROUND: The federal state of Saarland (SL) is experiencing the fastest demographic change in the western part of Germany. In this study, we analyzed retrospective data on the current and future supply of red blood cell concentrates (RBC) in this region and compared it to the current and future RBC demand in SL hospitals. METHODS: The projection of the SL blood supply in 2030 was modeled based on SL demographics for age distribution and donation frequency of donors, and the RBC transfusion data for in-house patients. These results were compared to published data on the transfusion demand from the state of Mecklenburg-Western Pomerania (MV). RESULTS: For the period January 1 to December 31, 2017, a total of 43,205 whole blood donations were collected. The donation frequency in SL never exceeded 80 per 1,000 inhabitants and was well below the numbers in MV. Thirty-one percent of the donors were responsible for 53.5% of the donations, and donors older than 45 years of age contributed highly to the total blood supply. In addition, 40,614 RBC transfusions at 10 SL hospitals were analyzed representing nearly all RBC transfusions for in-house patients in this region. RBC transfusions per 1,000 inhabitants increased with age from 24 (50-54) to 140 (80-84) years. Facing an already existing structural deficit of nearly 8,200 RBC in 2017, the projection predicts a dramatic increase in the regional deficit to >18,300 RBC in 2030. CONCLUSION: Our results on RBC demand in SL are comparable but not identical to those projected for the region of MV in eastern Germany. Due to the ongoing demographic changes in Germany as a whole, regular regional monitoring of RBC demand and the age structure of blood recipients and donors should be implemented to allow for better strategic planning in blood transfusion services and hospitals.

[Evaluation of Quality Indicators of Evidence-Based Guidelines Using ADT/GEKID Base Dataset and its Organ-Specific Modules]. / Berechenbarkeit der Qualitätsindikatoren der onkologischen S3-Leitlinien mit dem ADT-/GEKID-Basisdatensatz und seiner Zusatzmodule.

AIM: According to the Cancer Screening and Registers Act (KFRG, §65c SGB V), clinical cancer registration in Germany has to be based on the consistent set of variables developed by the "Association of German Tumor Centers" (ADT) and "Association of Population-based Cancer Registries in Germany" (GEKID) to improve oncological care. Quality indicators in evidence-based guidelines are measures to assess the quality of treatment and outcome in clinical care. The aim of this study was to find out the extent to which it is possible to determine these quality indicators using the ADT/GEKID's set of variables and the organ-specific modules. METHODS: After screening all available evidence-based guidelines for inclusion and exclusion criteria to calculate quality indicators, we evaluated for each indicator whether it can be computed using a single variable or a combination of variables of the ADT/GEKID's base variables set and the organ-specific modules. RESULTS: A total of 151 quality indicators were defined in 17 available evidence-based guidelines. Of these, 82 (54%) quality indicators could be determined with the variables of the base dataset. The highest proportion of calculable quality indicators was 100% for pancreatic cancer, which, however, was the only entity where all indicators were calculable. The least proportion of quality indicators was calculable for cancer of the oral cavity (10%). CONCLUSIONS: This analysis shows considerable differences in the possibility to evaluate the quality indicators defined in S3-guidelines for different tumor entities based on the variables documented in the clinical cancer registries throughout Germany. The ADT/GEKID core variables set should be extended with additional modules, for instance, for colorectal cancer, to allow a complete documentation of all criteria needed for the determination of clinical quality indicators as suggested in the pertinent evidence-based guidelines.

Characteristics of Recipients of Red Blood Cell Concentrates in a German Federal State.

BACKGROUND: Annual transfusion rates in many European countries range between 25 and 35 red blood cell concentrates (RBCs)/1,000 population. It is unclear why transfusion rates in Germany are considerably higher (approx. 50-55 RBCs/1,000 population). METHODS: We assessed the characteristics of transfusion recipients at all hospitals of the German federal state Mecklenburg-Western Pomerania during a 10-year longitudinal study. RESULTS: Although 75% of patients received ≤4 RBCs/patient in 2015 (1 RBC: 11.3%; 2 RBCs: 42.6%; 3 RBCs: 6.3%; 4 RBCs: 15.0%), the mean transfusion index was 4.6 RBCs due to a minority of patients with a high transfusion demand. Two thirds of all RBCs were transfused to only 25% of RBC recipients. Consistently, male patients received a higher number of RBCs (2005: 54.2%; 2015: 56.8%) and had a higher mean transfusion index than female patients (mean 5.1 ± 7.2; median 2; inter-quartile range [IQR] 2-4 vs. mean 4.0 ± 5.8; median 2; IQR 2-4). The absolute transfusion demand decreased between 2005 and 2015 by 13.5% due to a composite of active reduction (clinical practice change) and population decline in the 65- to 75-year age group (lower birth rate cohort 1940-1950); however, with major differences between hospitals (range from -61.0 to +41.4%). CONCLUSION: Transfusion demand in a population could largely be driven by patients with high transfusion demand. Different treatment practices in this group of patients probably add to the major differences in transfusion demand per 1,000 individuals between countries. The available data cannot prove this hypothesis. Implementation of a diagnosis-related group-based monitoring system is urgently needed to allow informative monitoring on the population level and meaningful comparisons between transfusion practices.

Correlation of gene expression and clinical parameters identifies a set of genes reflecting LV systolic dysfunction and morphological alterations.

To gain new insights into the complex pathophysiology of dilated cardiomyopathy (DCM) we performed a quantitative approach to identify genes with expression patterns that linearly correlate with parameters of cardiac morphology (left ventricular end-diastolic diameter indexed by body surface are (LVEDDI), systolic function [LV ejection fraction (LVEF)], and serum levels of cardiac peptide hormone NH2-terminal probrain natriuretic peptide (NT-proBNP) in human endomyocardial biopsies of 47 DCM patients and eight individuals with normal LVEF. A set of genes was identified as common heart failure markers characterized by correlation of their expression with cardiac morphology, systolic function, and NT-proBNP. Among them are already known genes encoding e.g., the natriuretic peptide hormones NPPA and NPPB and its converting enzyme corin, but also potential new heart failure markers like EP300 antisense RNA1 and dimethylarginine dimethylaminohydrolase 1 (DDAH1) along with other genes with so far unknown relation to heart function. In contrast, the expression of other genes including the Ca2+ flux regulating genes phospholamban (PLN), sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA), and extracellular matrix proteins showed significant correlation with LVEF and LVEDDI only. Those genes seem to reflect more specifically pathological alterations of systolic function and morphology in DCM hearts.

Longitudinal Changes in the Blood Supply and Demand in North-East-Germany 2005-2015.

BACKGROUND: Securing future blood supply is a major issue of transfusion safety. In this prospective 10-year longitudinal study we enrolled all blood donation services and hospitals of the federal state Mecklenburg-Western Pomerania. METHODS AND RESULTS: From 2005 to 2015 (time period with major demographic effects), whole blood donation numbers declined by 18%. In male donors this paralleled the demographic change, while donation rates of females declined 12.4% more than expected from demography. In parallel, red cell transfusion rates/1,000 population decreased from 2005 to 2015 from 56 to 51 (-8.4%), primarily due to less transfusions in patients >60 years. However, the transfusion demand declined much less than blood donation numbers: -13.5% versus -18%, and the population >65 years (highest transfusion demand) will further increase. The key question is whether the decline in transfusion demand observed over the previous years will further continue, hereby compensating for reduced blood donation numbers due to the demographic change. The population structure of Mecklenburg-Western Pomerania reflects all Eastern German federal states, while the Western German federal states will reach similar ratios of age groups 18-64 years / ≥65 years about 10 years later. CONCLUSIONS: Regular monitoring of age- and sex-specific donation and transfusion data is urgently required to allow transfusion services strategic planning for securing future blood supply.

Changes of myocardial gene expression and protein composition in patients with dilated cardiomyopathy after immunoadsorption with subsequent immunoglobulin substitution.

Immunoadsorption with subsequent immunoglobulin substitution (IA/IgG) represents a therapeutic approach for patients with dilated cardiomyopathy (DCM). Here, we studied which molecular cardiac alterations are initiated after this treatment. Transcription profiling of endomyocardial biopsies with Affymetrix whole genome arrays was performed on 33 paired samples of DCM patients collected before and 6 months after IA/IgG. Therapy-related effects on myocardial protein levels were analysed by label-free proteome profiling for a subset of 23 DCM patients. Data were analysed regarding therapy-associated differences in gene expression and protein levels by comparing responders (defined by improvement of left ventricular ejection fraction ≥20 % relative and ≥5 % absolute) and non-responders. Responders to IA/IgG showed a decrease in serum N-terminal proBNP levels in comparison with baseline which was accompanied by a decreased expression of heart failure markers, such as angiotensin converting enzyme 2 or periostin. However, despite clinical improvement even in responders, IA/IgG did not trigger general inversion of DCM-associated molecular alterations in myocardial tissue. Transcriptome profiling revealed reduced gene expression for connective tissue growth factor, fibronectin, and collagen type I in responders. In contrast, in non-responders after IA/IgG, fibrosis-associated genes and proteins showed elevated levels, whereas values were reduced or maintained in responders. Thus, improvement of LV function after IA/IgG seems to be related to a reduced gene expression of heart failure markers and pro-fibrotic molecules as well as reduced fibrosis progression.

A population-based longitudinal study on the implications of demographics on future blood supply.

BACKGROUND: Changes in demographics with increases in older age groups and decreases in younger age groups imply an increased demand for blood transfusions paralleled by a decrease in the population eligible for blood donation. However, more restrictive transfusion triggers and the patient blood management initiative also reduce the demand for red blood cells (RBCs). Eastern Germany is a model region for the impact of demographic changes, which manifest in this region approximately 10 years earlier than in other regions due to the 50% birth rate decline after 1989. STUDY DESIGN AND METHODS: We report the 2010 longitudinal 5-year follow-up of the study assessing all whole blood donations and RBC transfusions in Mecklenburg-West Pomerania. We compared the projections that were made 5 years ago with: 1) the current age structure of the blood donor and transfusion recipient populations and 2) its impact on blood demand and blood donation numbers in specific age groups. RESULTS: Transfusion rates were lower and blood donation rates were higher than predicted in 2005. Although transfusion rates/1000 decreased in nearly all age groups, the overall annual transfusion rate increased to 66.4 RBC units/1000 (in 2005, 62.2/1000) due to the absolute increase in the elderly population. Despite a 7.4% decline in the population 18 to 65 years of age, whole blood donations increased by 11.7% between 2005 and 2010, but thereafter decreased by 21% (first-time donors by 39.4%), reflecting the effect of the post-1990 birth rate decline on the donor population. CONCLUSION: Changes in demography and medical practice impact the delicate balance between available blood supply and potential future transfusion needs. In times of pronounced demographic changes, regular monitoring of the blood demand and age structure of blood recipients and donors is required to allow strategic planning to prevent blood shortages or overproduction.

Influence of reproductive history and exogenous hormone use on prevalence and frequency of circulating t(14;18)-positive cells in a population-based cross-sectional study.

PURPOSE: The t(14;18) translocation might represent an intermediate step in the pathogenesis of follicular lymphoma (FL), one of the most common subtypes of non-Hodgkin lymphoma. Circulating t(14;18)-positive cells can also be detected in 30-60 % of healthy individuals at low frequencies. Some studies found a negative association between reproductive factors or use of menopausal hormone therapy (MHT) with FL. The objective of this study was to evaluate whether there is an association between number of frequencies, oral contraceptive (OC) use, menopausal status and MHT, and t(14;18) prevalence and frequency in a representative population analysis based on an epidemiologic study in the northeastern part of Germany. METHODS: The analysis is based on results of buffy coat samples from 1,981 women of the Study of Health in Pomerania (SHIP-0) and data obtained in standardized face-to-face interviews. For prevalence, odds ratios (OR) and 95 % confidence intervals (CI) were calculated using unconditional logistic regression. Frequency data were analyzed using negative binomial regression. The multivariable models included age, number of pregnancies, menopausal status (premenopausal, natural, medical/surgical menopause), OC use and MHT as a measure for exogenous hormone exposure use. RESULTS: We found no association between reproductive history and combined exogenous hormone use on the prevalence of circulating t(14;18)-positive cells. Modeling MHT and OC use separately in a sensitivity analysis, the MHT parameter yielded statistical significance [OR 1.37 (95 % CI 1.04;1.81)]. t(14;18) frequency was associated with use of OC [incidence rate ratio (IRR) for ever use 3.18 (95 % CI 1.54;6.54)], current use [IRR 3.86 (1.56;9.54)], >10 years use [IRR 3.93 (1.67;9.23)] and MHT [restricted to postmenopausal women; IRR 2.63 (95 % CI 1.01;6.85)] in bivariate age-adjusted analyses. In the multivariable model, medical/surgical menopause [IRR 2.46 (1.11;5.44)] and the category ever use of OC and MHT were statistically significant [IRR 2.41 (1.09;5.33)]. CONCLUSIONS: Exogenous hormone use might be a risk factor for t(14;18) frequency rather than for t(14;18) prevalence. Further research on healthy individuals carrying a t(14;18) translocation and possible risk factors for malignant lymphoma is necessary to determine the additional molecular or immunological events that have to occur to develop FL.

Stiffness of left ventricular cardiac fibroblasts is associated with ventricular dilation in patients with recent-onset nonischemic and nonvalvular cardiomyopathy.

BACKGROUND: Ventricular dilation is known as a pivotal predictor in recent-onset cardiomyopathy (ROCM), but its pathophysiology is not fully understood. In the present study we investigated whether single-cell stiffness of right and left ventricular-derived fibroblasts has an effect on cardiac phenotype in patients with ROCM. METHODS AND RESULTS: Patients with endomyocardial biopsy-proven ROCM were included (n=10). Primary cardiac fibroblasts (CFBs) were cultured from left and right ventricular endomyocardial biopsies and their single-cell stiffness was analyzed by quantification of Young's modulus using colloidal probe atomic force microscopy. Cardiac fibrosis was analyzed by Masson's trichrome staining. CFBs from the left ventricle showed significantly decreased stiffness when compared with CFBs from the right ventricle, indexed by decreased stiffness (Young's modulus 3,374±389 vs. 4,837±690 Pa; P<0.05). Young's modulus of CFBs derived from the left ventricle correlated negatively with the left ventricular end-diastolic dimension derived from 2-dimensional echocardiography (R(2)=0.77; P<0.01). Neither left nor right ventricular fibrosis correlated with the respective ventricular dimensions. CONCLUSIONS: Our data suggest that a decrease in single-cell stiffness of left ventricular fibroblasts could trigger left ventricular dilation in patients with ROCM. This implies a new potential mechanism for the ventricular dilation with this disease.

Impact of physicians' attitude to vaccination on local vaccination coverage for pertussis and measles in Germany.

BACKGROUND: Vaccination rates of children in Germany are unsatisfying and regional endemic outbreaks have been reported. Few studies have analysed physicians' attitude towards vaccination. We investigated whether there is an association between physicians' attitude and vaccination coverage on the regional level for Germany. METHODS: In a representative cross-sectional survey, anonymized questionnaires were sent to random samples of all paediatricians (50%) and general practitioners (10%) in private practice in Germany. Attitude towards vaccination was operationalized in three scores. Measles and pertussis vaccination coverage rates were obtained from the 16 Federal States' Health Departments. Geographic methods and linear regression models were used for analysis. RESULTS: A total of 2010 paediatricians (response proportion: 64.1%) and 1712 general practitioners (response proportion 39.1%) were included in the analysis. We found an association of physicians' attitude towards vaccination and vaccination coverage rate (P < 0.0001). There is also an important association between vaccination coverage and the geographic location, with lower coverage rates especially in the States of former Western Germany (compared with our reference State Mecklenburg-Western Pomerania; pertussis: maximum -5.86% in Bavaria, P < 0.0001; measles: maximum -20.20% in Berlin, P = 0.0002). CONCLUSIONS: The regional association between vaccination coverage rates and physicians' attitude towards vaccination seems to be superposed by population-related variables. An increase of vaccination coverage requires better information and training of both, physicians and the general population.