Caregiver burden in partners of Heart Failure patients; limited influence of disease severity

BACKGROUND: In complying with required life style changes Heart Failure (HF) patients often depend on their partners. However providing care may cause burden and affect the health of these partners. The aim of this study was to investigate determinants of caregiver burden in order to identify caregivers who are at risk. METHODS: Using a cross-sectional design, caregiver burden and potential determinants were measured in partners of HF patients. Demographic and clinical data were assessed in HF patients, partners completed questionnaires on caregiver burden (the Caregiver Reaction Assessment, CRA), caregiving tasks performed, physical and mental health status and quality of the marital relationship. RESULTS: In total 357 partners (75% female, mean age 67 years) participated. The physical health status of HF patients was only significantly associated with two domains of caregiver burden, 'disruption of daily schedule' (p<0.01) and 'loss of physical strength' (p<0.01). No associations were found with age, co-morbidity and LVEF. All domains of the CRA were mainly associated with the partner's own mental health (p<0.01) and with providing personal care to HF patients (p<0.01). Gender differences were only found with regard to the domain of 'feeling a lack of family support'. CONCLUSION: The assessment of caregiver burden should focus on the mental strength of partners. Furthermore when assistance in personal care is needed, additional support, either informal or professional, may be indicated.     

Anxiolytic-like effect of 5-HT(2) ligands and benzodiazepines co-administration: comparison of two animal models of anxiety (the four-plate test and the elevated plus maze)

Animal models of anxiety remain a useful tool for evaluating the anxiolytic-like effect of new treatments. Even though many tests are similarly based on exploration tasks, using more than one animal model is all the more recommended since there are qualitative differences between such tests. Furthermore, although many tests are excellent tool for detecting benzodiazepines/GABA compounds, inconsistent results have been reported for 5-HT ligands. Here, two animal models have been chosen, the elevated plus maze (EPM) based on the natural aversion of rodents for open spaces and the four-plates test (FPT) a models involving the animal's conditioned response to stressful events. In a recent study, we have demonstrated that the 5-HT(2A/2C) agonist DOI and the 5-HT(2B) agonist BW 723C86 were shown to produce an anxiolytic-like effect in both tests. This study aimed to evaluate a putative interaction between benzodiazepine and 5-HT(2) ligands in the FPT and the EPM. Indeed, close distribution of GABA(A) and 5-HT(2) receptors was found in brain structures leading to functional interrelation. In the FPT, sub-active doses of alprazolam and diazepam were strongly potentiated by DOI. BW 723C86, also potentiated the anxiolytic-like effect of the two benzodiazepines with a weaker effect. In the same way, DOI and benzodiazepines administration induced an increase in the anxiolytic-like parameters in the EPM with a strongest effect observed with alprazolam. Regardless of anxiety models used in this study, 5-HT(2A) ligands exerted facilitatory influence upon GABAergic system. Therefore, the FPT and the EPM might implicate the same kind of anxiety.     

Absolute annual incidences of first events of venous thromboembolism and arterial vascular events in individuals with elevated FVIII:c. A prospective family cohort study

Elevated levels of factor VIII:c (elevated FVIII:c) are associated with an increased risk for venous thromboembolism (VTE) and arterial vascular events, and are at least in part determined genetically. We prospectively followed 192 asymptomatic individuals with elevated FVIII:c (>150%) and 340 with normal levels for an average duration of 31 months (range 7 to 56 months) to investigate the risk of VTE and arterial vascular events. Participants were first degree relatives of consecutive patients with elevated FVIII:c and VTE or arterial vascular events before the age of 50 years. The incidences of VTE were 1.25% (0.46-2.73) per year in the subjects with elevated FVIII:c, versus 0.23% (0.03-0.82) in those with normal levels (OR 5.5 [1.1-27.3]). The annual incidences of arterial vascular events were 1.04% (0.34-2.42) and 0.23% (0.03-0.82) in relatives with and without elevated levels of FVIII:c, respectively (OR: 4.5 [0.9-23.5]). After adjustment for age, smoking, known diabetes mellitus, hyperlipidemia, and hypertension, the odds ratio for any event was 3.7 (1.1-13.1). In conclusion, asymptomatic individuals with elevated FVIII:c levels and a positive family history of VTE or arterial vascular events before the age of 50 appear to have a high annual incidence of first VTE and arterial vascular events. Elevated FVIII:c may be a common risk factor for both clinical entities.     

The effect of substrate stiffness on adult neural stem cell behavior

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal and differentiation. In order to better understand the contribution of substrate stiffness to neural stem/progenitor cell (NSPC) differentiation and proliferation, a photopolymerizable methacrylamide chitosan (MAC) biomaterial was developed. Photopolymerizable MAC is particularly compelling for the study of the central nervous system stem cell niche because Young's elastic modulus (E_Y) can be tuned from less than 1 kPa to greater than 30 kPa. Additionally, the numerous free amine functional groups enable inclusion of biochemical signaling molecules that, together with the mechanical environment, influence cell behavior. Herein, NSPCs proliferated on MAC substrates with Young's elastic moduli below 10 kPa and exhibited maximal proliferation on 3.5 kPa surfaces. Neuronal differentiation was favored on the softest surfaces with E_Y < 1 kPa as confirmed by both immunohistochemistry and qRT-PCR. Oligodendrocyte differentiation was favored on stiffer scaffolds (>7 kPa); however, myelin oligodendrocyte glycoprotein (MOG) gene expression suggested that oligodendrocyte maturation and myelination was best on <1 kPa scaffolds where more mature neurons were present. Astrocyte differentiation was only observed on <1 and 3.5 kPa surfaces and represented less than 2% of the total cell population. This work demonstrates the importance of substrate stiffness to the proliferation and differentiation of adult NSPCs and highlights the importance of mechanical properties to the success of scaffolds designed to engineer central nervous system tissue.     

Current Practice in Meeting Child Health Needs in Family Support Services: Variation by Service Type and Perspectives on Future Developments

The needs of all service users include those related to physical, emotional, sexual and mental health. This article documents where child health needs are recognised and being met within family support services in the west of Ireland, investigates whether there is variation across different types of family support services and presents the views of service providers as to how health needs could be more fully addressed. Four randomly selected service managers were interviewed; followed by a census survey of managers within the region. Thirty-three managers returned questionnaires (80% response) on their formal briefs in relation to health, perceived health needs being met and unmet, approaches to meeting health needs and resources required to adequately meet client health needs. Emotional and mental health needs were most frequently being met within current services, while group work, one-to-one work and referring on were all popular approaches. Systematic differences emerged by service size and client group. Access to expertise and staff training were perceived as the most popular approaches to improving service provision. These data illustrate that there is a need to develop guidelines for practice, foster links between services and provide for specialised staff training in relation to child health issues.     

HPLC methods for the purification of [11C]‐labelled radiopharmaceuticals: reversal of the retention order of products and precursors

Preparative HPLC methods have been developed for a number of [¹¹C]‐methylated PET tracers, which enable elution of the labelled compounds prior to their precursors, thus reducing the overall synthesis time and avoiding contamination of the final product with precusor. This reversal of retention order has been achieved for [¹¹C]DASB, [¹¹C]raclopride, [¹¹C]FLB 457, [¹¹C]carfentanil, and 2‐fluoro‐[N‐methyl‐¹¹C]apomorphine, enabling collection of the purified radiopharmaceuticals from the HPLC system after 5–7 min. Furthermore, by using ethanol as the organic modifier, residual solvent analysis prior to human injection could be avoided and three of the radiopharmaceuticals could be injected directly following simple dilution and sterile filtration. Copyright © 2009 John Wiley & Sons, Ltd.     

Expression and prognostic significance of a panel of tissue hypoxia markers in head-and-neck squamous cell carcinomas

PURPOSE: To investigate the expression pattern of hypoxia-induced proteins identified as being involved in malignant progression of head-and-neck squamous cell carcinoma (HNSCC) and to determine their relationship to tumor pO(2) and prognosis. METHODS AND MATERIALS: We performed immunohistochemical staining of hypoxia-induced proteins (carbonic anhydrase IX [CA IX], BNIP3L, connective tissue growth factor, osteopontin, ephrin A1, hypoxia inducible gene-2, dihydrofolate reductase, galectin-1, IkappaB kinase beta, and lysyl oxidase) on tumor tissue arrays of 101 HNSCC patients with pretreatment pO(2) measurements. Analysis of variance and Fisher's exact tests were used to evaluate the relationship between marker expression, tumor pO(2), and CA IX staining. Cox proportional hazard model and log-rank tests were used to determine the relationship between markers and prognosis. RESULTS: Osteopontin expression correlated with tumor pO(2) (Eppendorf measurements) (p = 0.04). However, there was a strong correlation between lysyl oxidase, ephrin A1, and galectin-1 and CA IX staining. These markers also predicted for cancer-specific survival and overall survival on univariate analysis. A hypoxia score of 0-5 was assigned to each patient, on the basis of the presence of strong staining for these markers, whereby a higher score signifies increased marker expression. On multivariate analysis, increasing hypoxia score was an independent prognostic factor for cancer-specific survival (p = 0.015) and was borderline significant for overall survival (p = 0.057) when adjusted for other independent predictors of outcomes (hemoglobin and age). CONCLUSIONS: We identified a panel of hypoxia-related tissue markers that correlates with treatment outcomes in HNSCC. Validation of these markers will be needed to determine their utility in identifying patients for hypoxia-targeted therapy.