The relevance of heart failure severity for treatment with evidence-based pharmacotherapy in general practice

AIMS: Internationally, research indicates that pharmacotherapy for chronic heart failure (CHF) is sub-optimal. Traditionally, assessment of drug use in heart failure has focused on the use of individual agents irrespective of CHF severity. This study investigates drug use for CHF patients in general practice with respect to the available evidence, incorporating both disease severity and the use of combination drug regimes. METHODS AND RESULTS: A cross-sectional survey of 769 Dutch CHF patients was performed as part of IMPROVEMENT of HF study. For each New York Heart Association severity classification the minimum treatment appropriate for the heart failure severity according to the scientific evidence available at the time of the study (1999) was defined. The proportion of patients treated with each drug increased with increasing severity, with the exception of the beta-blockers. Patients with less severe heart failure were approximately four to eight times more likely to receive evidence-based treatment than those with more severe heart failure. DISCUSSION: To assess pharmacological treatment of heart failure, in relation to the available evidence, it is important to take severity into account. While the number of drugs prescribed increased with increasing severity, the use of evidence-based regimes was lower in patients with more severe heart failure.     

A neurosurgical phantom-based training system with ultrasound simulation

Background

Brain tumor surgeries are associated with a high technical and personal effort. The required interactions between the surgeon and the technical components, such as neuronavigation, surgical instruments and intraoperative imaging, are complex and demand innovative training solutions and standardized evaluation methods. Phantom-based training systems could be useful in complementing the existing surgical education and training.

Methods

A prototype of a phantom-based training system was developed, intended for standardized training of important aspects of brain tumor surgery based on real patient data. The head phantom consists of a three-part construction that includes a reusable base and adapter, as well as a changeable module for single use. Training covers surgical planning of the optimal access path, the setup of the navigation system including the registration of the head phantom, as well as the navigated craniotomy with real instruments. Tracked instruments during the simulation and predefined access paths constitute the basis for the essential objective training feedback.

Results

The prototype was evaluated in a pilot study by assistant physicians at different education levels. They performed a complete simulation and a final assessment using an evaluation questionnaire. The analysis of the questionnaire showed the evaluation result as “good” for the phantom construction and the used materials. The learning effect concerning the navigated planning was evaluated as “very good”, as well as having the effect of increasing safety for the surgeon before planning and conducting craniotomies independently on patients.

Conclusions

The training system represents a promising approach for the future training of neurosurgeons. It aims to improve surgical skill training by creating a more realistic simulation in a non-risk environment. Hence, it could help to bridge the gap between theoretical and practical training with the potential to benefit both physicians and patients.     

Stage‐specific requirement for cyclin D1 in glial progenitor cells of the cerebral cortex

Despite the vast abundance of glial progenitor cells in the mouse brain parenchyma, little is known about the molecular mechanisms driving their proliferation in the adult. Here we unravel a critical role of the G1 cell cycle regulator cyclin D1 in controlling cell division of glial cells in the cortical grey matter. We detect cyclin D1 expression in Olig2‐immunopositive (Olig2+) oligodendrocyte progenitor cells, as well as in Iba1+ microglia and S100β+ astrocytes in cortices of 3‐month‐old mice. Analysis of cyclin D1‐deficient mice reveals a cell and stage‐specific molecular control of cell cycle progression in the various glial lineages. While proliferation of fast dividing Olig2+ cells at early postnatal stages becomes gradually dependent on cyclin D1, this particular G1 regulator is strictly required for the slow divisions of Olig2+/NG2+ oligodendrocyte progenitors in the adult cerebral cortex. Further, we find that the population of mature oligodendrocytes is markedly reduced in the absence of cyclin D1, leading to a significant decrease in the number of myelinated axons in both the prefrontal cortex and the corpus callosum of 8‐month‐old mutant mice. In contrast, the pool of Iba1+ cells is diminished already at postnatal day 3 in the absence of cyclin D1, while the number of S100β+ astrocytes remains unchanged in the mutant. GLIA 2014;62:829–839     

Allergen Content of Therapeutic Preparations for Allergen-Specific Immunotherapy of European Paper Wasp Venom Allergy

Allergy to Polistes dominula (European paper wasp) venom is of particular relevance in Southern Europe, potentially becoming a threat in other regions in the near future, and can be effectively cured by venom immunotherapy (VIT). As allergen content in extracts may vary and have an impact on diagnostic and therapeutic approaches, the aim was to compare five therapeutic preparations for VIT of P. dominula venom allergy available in Spain. Products from five different suppliers were analyzed by SDS-PAGE and LC-MS/MS and compared with a reference venom sample. Three products with P. dominula venom and one product with a venom mixture of American Polistes species showed a comparable band pattern in SDS-PAGE as the reference sample and the bands of the major allergens phospholipase A1 and antigen 5 were assignable. The other product, which consists of a mixture of American Polistes species, exhibited the typical band pattern in one, but not in another sample from a second batch. All annotated P. dominula allergens were detected at comparable levels in LC-MS/MS analysis of products containing P. dominula venom. Due to a lack of genomic information on the American Polistes species, the remaining products were not analyzed by this method. The major Polistes allergens were present in comparable amounts in the majority, but not in all investigated samples of venom preparations for VIT of P. dominula venom allergy.     

Larger amygdala volumes in first depressive episode as compared to recurrent major depression and healthy control subjects.

BACKGROUND: The aim of our study was to test the hypothesis that amygdala volumes are reduced in patients with recurrent major depression compared with first episode patients. METHODS: Using structural magnetic resonance imaging, we compared 30 inpatients with first-episode depression and 27 inpatients with recurrent major depression (DSM-IV) with healthy volunteer subjects from the local community matched for age, gender, and handedness. RESULTS: Patients with first-episode depression showed enlarged amygdala volumes compared with patients with recurrent major depression and healthy control subjects. No significant differences were found between patients with recurrent depression and healthy control subjects. No significant correlations were found between amygdala volumes and age of onset, illness duration, or severity of depression. CONCLUSIONS: Larger amygdala volumes in patients with first-episode depression may result from higher amygdala metabolism and blood flow. Additionally, disease progression with stress-related excitotoxic processes during recurrent depressive episodes might result in decreased amygdala volumes. Prospective investigations to investigate amygdala changes during the course of depression are needed.     

A Novel Angiographic Quantification of Aortic Regurgitation After TAVR Provides an Accurate Estimation of Regurgitation Fraction Derived From Cardiac Magnetic Resonance Imaging

Objectives

This study sought to compare a new quantitative angiographic technique to cardiac magnetic resonance-derived regurgitation fraction (CMR-RF) for the quantification of prosthetic valve regurgitation (PVR) after transcatheter aortic valve replacement (TAVR).

Increased Heparanase Levels in Urine during Acute Puumala Orthohantavirus Infection Are Associated with Disease Severity

Old–world orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS), characterized by acute kidney injury (AKI) with transient proteinuria. It seems plausible that proteinuria during acute HFRS is mediated by the disruption of the glomerular filtration barrier (GFB) due to vascular leakage, a hallmark of orthohantavirus–caused diseases. However, direct infection of endothelial cells by orthohantaviruses does not result in increased endothelial permeability, and alternative explanations for vascular leakage and diminished GFB function are necessary. Vascular integrity is partly dependent on an intact endothelial glycocalyx, which is susceptible to cleavage by heparanase (HPSE). To understand the role of glycocalyx degradation in HFRS–associated proteinuria, we investigated the levels of HPSE in urine and plasma during acute, convalescent and recovery stages of HFRS caused by Puumala orthohantavirus. HPSE levels in urine during acute HFRS were significantly increased and strongly associated with the severity of AKI and other markers of disease severity. Furthermore, increased expression of HPSE was detected in vitro in orthohantavirus–infected podocytes, which line the outer surfaces of glomerular capillaries. Taken together, these findings suggest the local activation of HPSE in the kidneys of orthohantavirus–infected patients with the potential to disrupt the endothelial glycocalyx, leading to increased protein leakage through the GFB, resulting in high amounts of proteinuria.     

Alumina‐reinforced zirconia implants: survival rate and fracture strength in a masticatory simulation trial

Background: Alumina‐toughened zirconia (ATZ) is a possible alternative material to titanium for oral implants. No data are available on the fracture strength of ATZ oral implants. Purpose: The purpose of this study was to examine one‐piece implants made of ATZ ceramic under artificial loading conditions and to compare the fracture strength of these implants with implants fabricated from tetragonal zirconium dioxide poylcrystal (TZP)‐A. Materials and methods: A total of 72 implants, 48 ATZ implants (groups A and B) and 24 TZP‐A implants (group C), were investigated. A chamfer preparation at the implant heads was performed on all implants of groups B and C. Eight implants of each group underwent 1.2 or five million thermomechanical loading cycles in the chewing simulator (load value: 98 N). Further eight implants of each group were not cyclic loaded. Finally, the fracture strength of all implants was determined using a universal testing machine. Results: No implant fractured during loading in the chewing simulator. All implants were placed in the universal testing machine to evaluate fracture strength. The mean fracture strength values±standard deviations for the implants without artificial loading were 1734±165 N (ATZ, no preparation), 1220±85 N (ATZ, with preparation), and 578±49 N (TZP‐A, with preparation); 1489±190 N (ATZ, no preparation), 1064±121 N (ATZ, with preparation), and 607±57 N (TZP‐A, with preparation) with 1.2 million loading cycles; and 1358±187 N (ATZ, no preparation), 1098±97 N (ATZ, with preparation), and 516±45 N (TZP‐A, with preparation) with five million cycles. The ATZ implants showed significantly higher mean fracture strengths compared with the TZP‐A implants. Modification of the implant head using diamond burs and increased loading time also led to a significant decrease in fracture strength. Conclusions: The ATZ implants showed an increased mechanical stability compared with the TZP‐A. Modification of the implant head resulted in a decrease in fracture strength. However, within the limits of this in vitro investigation it can be concluded that ATZ implants will withstand functional loading over an estimated period of 20 years. To cite this article:
Kohal R‐J, Wolkewitz M, Mueller C. Alumina‐reinforced zirconia implants: survival rate and fracture strength in a masticatory simulation trial.
Clin. Oral Impl. Res. 21 , 2010; 1345–1352.
doi: 10.1111/j.1600‐0501.2010.01954.x     

Predictors of treatment outcomes after removal of amalgam fillings: associations between subjective symptoms,psychometric variables and mercury levels

Weidenhammer W, Bornschein S, Zilker T, Eyer F, Melchart D, Hausteiner C. Predictors of treatment outcomes after removal of amalgam fillings: associations between subjective symptoms, psychometric variables and mercury levels. Community Dent Oral Epidemiol 2010. © 2010 John Wiley & Sons A/S Abstract – Objective: This analysis aimed to study predictors of different treatment outcomes and associations between subjective symptoms, psychometric variables and mercury levels in patients who subjectively attributed their health problems to dental amalgam. Material and methods: A secondary and retrospective analysis of data of a recently published randomized clinical trial was performed. Seventy‐eight patients [44% female, mean (SD) age 35 (6) years, randomly assigned to either amalgam removal or a health promotion program] were included into statistical analysis. Prior to intervention and 12 months later, questionnaires for assessing symptoms, psychological distress and health status were presented, and mercury levels in blood and urine were determined. Results: The patients’ personality profile at study onset was characterized by slightly reduced extraversion and slightly elevated emotional instability. Overall, subjective symptoms decreased slightly and there were no statistically significant differences in the decrease of symptoms after intervention between both groups. Decrease of mercury levels after intervention was closely associated with removal of amalgam fillings (r_mult = 0.64 in regression analysis). Statistically significant correlations could be found between mercury levels and subjective symptoms with respect to baseline (r = 0.29–0.39) and to changes after intervention (r = 0.24–0.42), but not for psychological distress (r = 0.05–0.25) and health related quality of life (r = ?0.03–0.18). Prediction of symptom improvement after intervention was poor (r_mult = 0.44). Conclusions: Results contribute some new aspects to the inconsistent findings in the literature with respect to associations between symptoms and subtoxic mercury levels. More emphasis should be placed on exploring individual vulnerability for amalgam sensitivity.