Multimorbidity and health-related quality of life in the older population: results from the German KORA-Age study

<p>Abstract</p> <p>Background</p> <p>Multimorbidity in the older population is well acknowledged to negatively affect health-related quality of life (HRQL). Several studies have examined the independent effects of single diseases; however, little research has focused on interaction between diseases. The purpose of this study was to assess the impact of six self-reported major conditions and their combinations on HRQL measured by the EQ-5D.</p> <p>Methods</p> <p>The EQ-5D was administered in the population-based KORA-Age study of 4,565 Germans aged 65 years or older. A generalised additive regression model was used to assess the effects of chronic conditions on HRQL and to account for the nonlinear associations with age and body mass index (BMI). Disease interactions were identified by a forward variable selection method.</p> <p>Results</p> <p>The conditions with the greatest negative impact on the EQ-5D index were the history of a stroke (regression coefficient -11.3, p < 0.0001) and chronic bronchitis (regression coefficient -8.1, p < 0.0001). Patients with both diabetes and coronary disorders showed more impaired HRQL than could be expected from their separate effects (coefficient of interaction term -8.1, p < 0.0001). A synergistic effect on HRQL was also found for the combination of coronary disorders and stroke. The effect of BMI on the mean EQ-5D index was inverse U-shaped with a maximum at around 24.8 kg/m².</p> <p>Conclusions</p> <p>There are important interactions between coronary problems, diabetes mellitus, and the history of a stroke that negatively affect HRQL in the older German population. Not only high but also low BMI is associated with impairments in health status.</p

Order specific fertility rates for Germany: Estimates from Perinatal Statistics for the period 2001-2008

Until 2008, Germany’s vital statistics did not include information on the biological order of each birth. This resulted in a dearth of important demographic indicators, such as the mean age at fi rst birth and the level of childlessness. Researchers have tried to fill this gap by generating order-specifi c birth rates from survey data, and by combining survey data with vital statistics. This paper takes a different approach by using Perinatal Statistics to generate birth order-specific fertility rates for the period 2001 to 2008. Perinatal Statistics includes information on births that took place in German hospitals. Out-of-hospital births, which account for about 2 % of all births, are not included in the Perinatal Statistics. In a sensitivity analysis, we show how robust our estimates are to the inclusion of out-of-hospital births. Our general assessment is that the Perinatal Statistics is a valuable source for generating order-specific fertility rates, regardless of whether out-of-hospital births are included

Evidence for a Relationship between VEGF and BMI Independent of Insulin Sensitivity by Glucose Clamp Procedure in a Homogenous Group Healthy Young Men

BACKGROUND: This is the first study to experimentally explore the direct relationship between circulating VEGF levels and body mass index (BMI) as well as to unravel the role of insulin sensitivity in this context under standardized glucose clamp conditions as the methodical gold-standard. In order to control for known influencing factors such as gender, medication, and arterial hypertension, we examined a highly homogeneous group of young male subjects. Moreover, to encompass also subjects beyond the normal BMI range, low weight and obese participants were additionally included and stress hormones as a main regulator of VEGF were assessed. METHODOLOGY/PRINCIPAL FINDINGS: Under euglycemic clamp conditions, VEGF was measured in 15 normal weight (BMI 20-25 kg/m(2)), 15 low weight (BMI<20 kg/m(2)), and 15 obese (BMI>30 kg/m(2)) male subjects aged 18-30 years and the insulin sensitivity index (ISI) was calculated. Since stress axis activation promotes VEGF secretion, concentrations of ACTH, cortisol, and catecholamines were monitored. Despite of comparable ACTH (P = 0.145), cortisol (P = 0.840), and norepinephrine (P = 0.065) levels, VEGF concentrations differed significantly between BMI-groups (P = 0.008) with higher concentrations in obese subjects as compared to normal weight (P = 0.061) and low weight subjects (P = 0.002). Pearson's correlation analysis revealed a positive relationship between BMI and VEGF levels (r = 0.407; P = 0.010) but no correlation of VEGF with ISI (r = 0.224; P = 0.175). CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a positive correlation between concentrations of circulating VEGF levels and BMI in healthy male subjects under highly controlled conditions. This relationship which is apparently disconnected from insulin sensitivity may be part of some pathogenetic mechanisms underlying obesity and type 2 diabetes

Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

Glycemic management in type 2 diabetes mellitus has become increasingly complex and, to some extent, controversial, with a widening array of pharmacological agents now available (1–5), mounting concerns about their potential adverse effects and new uncertainties regarding the benefits of intensive glycemic control on macrovascular complications (6–9). Many clinicians are therefore perplexed as to the optimal strategies for their patients. As a consequence, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a joint task force to examine the evidence and develop recommendations for antihyperglycemic therapy in nonpregnant adults with type 2 diabetes. Several guideline documents have been developed by members of these two organizations (10) and by other societies and federations (2,11–15). However, an update was deemed necessary because of contemporary information on the benefits/risks of glycemic control, recent evidence concerning efficacy and safety of several new drug classes (16,17), the withdrawal/restriction of others, and increasing calls for a move toward more patient-centered care (18,19). This statement has been written incorporating the best available evidence and, where solid support does not exist, using the experience and insight of the writing group, incorporating an extensive review by additional experts (acknowledged below). The document refers to glycemic control; yet this clearly needs to be pursued within a multifactorial risk reduction framework. This stems from the fact that patients with type 2 diabetes are at increased risk of cardiovascular morbidity and mortality; the aggressive management of cardiovascular

Strong electron-phonon coupling and enhanced phonon Gr\"uneisen parameters in valence-fluctuating metal EuPd2_2Si2_2

We study the valence crossover and strong electron-phonon coupling of EuPd$_2$Si$_2$ by polarization-resolved Raman spectroscopy. The fully-symmetric phonon mode shows strongly asymmetric lineshape at low temperature, indicating Fano-type interaction between this mode and a continuum of electron-hole excitations. Moreover, the frequency and linewidth of the phonon modes exhibit anomalies across the valence-crossover temperature, suggesting the coupling between valence fluctuations and lattice vibration. In particular, two phonon modes show significantly enhanced Gr\"uneisen parameter, suggesting proximity to a critical elasticity regime. The relative contribution of the structural change and valence change to the phonon anomalies is evaluated by density functional theory calculations

Mesenchymal stromal cells for treatment of steroid-refractory GvHD : a review of the literature and two pediatric cases

Severe acute graft versus host disease (GvHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. Human mesenchymal stromal cells (MSCs) play an important role in endogenous tissue repair and possess strong immune-modulatory properties making them a promising tool for the treatment of steroid-refractory GvHD. To date, a few reports exist on the use of MSCs in treatment of GvHD in children indicating that children tend to respond better than adults, albeit with heterogeneous results. We here present a review of the literature and the clinical course of two instructive pediatric patients with acute steroid-refractory GvHD after haploidentical stem cell transplantation, which exemplify the beneficial effects of third-party transplanted MSCs in treatment of acute steroid-refractory GvHD. Moreover, we provide a meta-analysis of clinical studies addressing the outcome of patients with steroid-refractory GvHD and treatment with MSCs in adults and in children (n = 183; 122 adults, 61 children). Our meta-analysis demonstrates that the overall response-rate is high (73.8%) and confirms, for the first time, that children indeed respond better to treatment of GvHD with MSCs than adults (complete response 57.4% vs. 45.1%, respectively). These data emphasize the significance of this therapeutic approach especially in children and indicate that future prospective studies are needed to assess the reasons for the observed differential response-rates in pediatric and adult patients. Additional file 1: MSCs expansion and release criteria.his file contains a detailed description of the MSCs expansion and release criteria for Case A and Case B

Population genomic analysis of elongated skulls reveals extensive female-biased immigration in Early Medieval Bavaria

Modern European genetic structure demonstrates strong correlations with geography, while genetic analysis of prehistoric humans has indicated at least two major waves of immigration from outside the continent during periods of cultural change. However, population-level genome data that could shed light on the demographic processes occurring during the intervening periods have been absent. Therefore, we generated genomic data from 41 individuals dating mostly to the late 5th/early 6th century AD from present-day Bavaria in southern Germany, including 11 whole genomes (mean depth 5.56×). In addition we developed a capture array to sequence neutral regions spanning a total of 5 Mb and 486 functional polymorphic sites to high depth (mean 72×) in all individuals. Our data indicate that while men generally had ancestry that closely resembles modern northern and central Europeans, women exhibit a very high genetic heterogeneity; this includes signals of genetic ancestry ranging from western Europe to East Asia. Particularly striking are women with artificial skull deformations; the analysis of their collective genetic ancestry suggests an origin in southeastern Europe. In addition, functional variants indicate that they also differed in visible characteristics. This example of female-biased migration indicates that complex demographic processes during the Early Medieval period may have contributed in an unexpected way to shape the modern European genetic landscape. Examination of the panel of functional loci also revealed that many alleles associated with recent positive selection were already at modern-like frequencies in European populations ∼1,500 years ago