Thoughts about encounters between nondisabled and disabled peers: Situational constraints,states-of-mind,valenced thought categories

This study explores three issues: thoughts and feelings of individuals with and without physical disabilities concerning encounters in different situations, ways of grouping self-statements into valenced categories, and use of states-of-mind (SOM) ratios as an alternative to positive and negative thought frequencies. Data from 127 able-bodied and 46 physically disabled college students indicate that, in everyday social encounters, nondisabled individuals' thoughts and feelings were more negative, while those of disabled individuals were more negative when helping was involved and when encounters centered on the impairment. Thus, problematic encounters between people with and without disabilities may be due to the reactions of individuals with disabilities in situations which involve help, and to reactions of able-bodied persons in everyday contexts. The data also confirm the utility of SOM ratios as an alternative to valenced frequencies in cognitive assessment: SOM scores discriminated groups when situational demands were manipulated and scores were linearly related to criterion measures. However, SOM ratios differed dramatically, depending on the attentional focus of thoughts. The findings illustrate types of thoughts which occur during interaction between people with and without disabilities, demonstrate a simple technique for grouping thoughts into valenced categories on an empirical basis, and highlight the relative contribution of cognitive and affective elements to overall valenced scores. Implications for research on assessment of self-statements are discussed and recommendations are made concerning programming to facilitate the social integration of people with disabilities.This research was supported by grants to the first author from the Social Sciences and Humanities Research Council of Canada and from Fonds F.C.A.R. pour l'aide et le soutien à la recherche. Thanks are due to Meribah Aikens, Maria Barile, Leo Bissonette, Bosco Daude, Jim Dubois, Lillian Fox, Evelyn Gold, Naomi Goodz, Darlene Judd, André Leblanc, John Martos, Sue McKenzie, Irwin Slopak, and Joan Wolforth for their assistance with various stages of this investigation.     

The epidemiology of peripheral vein infusion thrombophlebitis: a critical review

We critically assessed studies on the clinical importance, diagnosis, incidence, and pathogenesis of peripheral vein infusion thrombophlebitis, including catheter-related and patient-related risk factors. We reviewed the evidence linking thrombosis, particularly prothrombotic states such as the inherited thrombophilic disorders, with peripheral vein infusion thrombophlebitis. Peripheral vein infusion thrombophlebitis occurs in 25% to 35% of hospitalized patients with peripheral intravenous catheters and has both patient-related implications (e.g., sepsis) and economic consequences (e.g., extra nursing time). Although duration of catheterization, catheter-related infection, and catheter material are important risk factors for peripheral vein infusion thrombophlebitis, patient-related risk factors are not well elucidated.     

Management of venous thromboembolism in cancer patients and the role of the new oral anticoagulants

Patients with cancer are at high risk for venous thromboembolism (VTE). Most clinical guidelines agree that low-molecular-weight heparins (LMWHs) are the preferred anticoagulants for the prevention and treatment of VTE in cancer patients. However, LMWHs require daily injections, weight-adjustment of dose, and can be associated with heparin-induced thrombocytopenia; all of which are important considerations in managing cancer-associated VTE. Comparatively, the new oral anticoagulants offer a more attractive option because of their oral administration, fixed-dose, and lack of routine laboratory monitoring. The results of phase III trials support the efficacy and safety of the new oral anticoagulants in the management of VTE. However, generalizing these findings to cancer patients with VTE is difficult since very few cancer patients were included. In this comprehensive review, we provide an overview of the current treatment of VTE, explore anticoagulant thromboprophylaxis in ambulatory cancer patients, and summarize existing evidence on the efficacy and safety of the new oral anticoagulants for the management of VTE in both non-cancer and cancer populations.     

Multifunctional,self-assembling anionic peptide-lipid nanocomplexes for targeted siRNA delivery

Formulations of cationic liposomes and polymers readily self-assemble by electrostatic interactions with siRNA to form cationic nanoparticles which achieve efficient transfection and silencing in vitro. However, the utility of cationic formulations in vivo is limited due to rapid clearance from the circulation, due to their association with serum proteins, as well as systemic and cellular toxicity. These problems may be overcome with anionic formulations but they provide challenges of self-assembly and transfection efficiency. We have developed anionic, siRNA nanocomplexes utilizing anionic PEGylated liposomes and cationic targeting peptides that overcome these problems. Biophysical measurements indicated that at optimal ratios of components, anionic PEGylated nanocomplexes formed spherical particles and that, unlike cationic nanocomplexes, were resistant to aggregation in the presence of serum, and achieved significant gene silencing although their non-PEGylated anionic counterparts were less efficient. We have evaluated the utility of anionic nanoparticles for the treatment of neuronal diseases by administration to rat brains of siRNA to BACE1, a key enzyme involved in the formation of amyloid plaques. Silencing of BACE1 was achieved in vivo following a single injection of anionic nanoparticles by convection enhanced delivery and specificity of RNA interference verified by 5′ RACE-PCR and Western blot analysis of protein.     

A comprehensive view of sex-specific issues related to cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of mortality in women. In fact, CVD is responsible for a third of all deaths of women worldwide and half of all deaths of women over 50 years of age in developing countries. The prevalence of CVD risk factor precursors is increasing in children. Retrospective analyses suggest that there are some clinically relevant differences between women and men in terms of prevalence, presentation, management and outcomes of the disease, but little is known about why CVD affects women and men differently. For instance, women with diabetes have a significantly higher CVD mortality rate than men with diabetes. Similarly, women with atrial fibrillation are at greater risk of stroke than men with atrial fibrillation. Historically, women have been underrepresented in clinical trials. The lack of good trial evidence concerning sex-specific outcomes has led to assumptions about CVD treatment in women, which in turn may have resulted in inadequate diagnoses and suboptimal management, greatly affecting outcomes. This knowledge gap may also explain why cardiovascular health in women is not improving as fast as that of men. Over the last decades, mortality rates in men have steadily declined, while those in women remained stable. It is also becoming increasingly evident that gender differences in cultural, behavioural, psychosocial and socioeconomic status are responsible, to various degrees, for the observed differences between women and men. However, the interaction between sex-and gender-related factors and CVD outcomes in women remains largely unknown.     

Integrin-targeted nanocomplexes for tumour specific delivery and therapy by systemic administration

Nanoparticle formulations offer opportunities for tumour delivery of therapeutic reagents. The Receptor-Targeted Nanocomplex (RTN) formulation consists of a PEGylated, endosomally-cleavable lipid and an RGD integrin-targeting, endosomally-cleavable peptide. Nancomplexes self-assemble on mixing with plasmid DNA to produce nanoparticles of about 100 nm. The environmentally-sensitive linkers promote intracellular disassembly and release of the DNA. RTNs carrying luciferase genes were administered intravenously to mice carrying subcutaneous neuroblastoma tumours. Luciferase expression was much higher in tumours than in liver, spleen and lungs while plasmid biodistribution studies supported the expression data. Transfection in tumours was enhanced two-fold by integrin-targeting peptides compared to non-targeted nanocomplexes. RTNs containing the interleukin-2 (IL-2) and IL-12 genes were administered intravenously with seven doses at 48 h intervals and tumour growth monitored. Tumours from treated animals were approximately 75% smaller on day 11 compared with RTNs containing control plasmids with one third of treated mice surviving long-term. Extensive leukocyte infiltration, decreased vascularization and increased necrotic areas were observed in the tumours from IL2/IL12 treated animals. Splenocytes from re-challenged mice displayed enhanced IL-2 production following Neuro-2A co-culture, which, combined with infiltration studies, suggested a cytotoxic T cell-mediated9 tumour-rejection process. The integrin-targeted RTN formulation may have broader applications in the further development of cancer therapeutics.     

Social Skills Training for Adolescents with Asperger Syndrome and High-Functioning Autism

The effectiveness of a social skills training group for adolescents with Asperger syndrome and high-functioning autism (AS/HFA) was evaluated. Parents of six groups of adolescents (n = 46, 61% male, mean age 14.6) completed questionnaires immediately before and after the 12-week group. Parents and adolescents were surveyed regarding their experience with the group. Significant pre- to post-treatment gains were found on measures of both social competence and problem behaviors associated with AS/HFA. Effect sizes ranged from .34 to .72. Adolescents reported more perceived skill improvements than did parents. Parent-reported improvement suggests that social skills learned in group sessions generalize to settings outside the treatment group. Larger, controlled studies of social skills training groups would be valuable.     

Multifunctional receptor-targeted nanocomplexes for magnetic resonance imaging and transfection of tumours

The efficient targeted delivery of nucleic acids in?vivo provides some of the greatest challenges to the development of genetic therapies. We aim to develop nanocomplex formulations that achieve targeted transfection of neuroblastoma tumours that can be monitored simultaneously by MRI. Here, we have compared nanocomplexes comprising self-assembling mixtures of liposomes, plasmid DNA and one of three different peptide ligands derived from ApoE, neurotensin and tetanus toxin for targeted transfection in?vitro and in?vivo. Neurotensin-targeted nanocomplexes produced the highest levels of transfection and showed a 4.7-fold increase in transfected luciferase expression over non-targeted nanocomplexes in Neuro-2A cells. Transfection of subcutaneous Neuro-2A tumours in?vivo with neurotensin-targeted nanocomplexes produced a 9.3-fold increase in gene expression over non-targeted controls. Confocal microscopy analysis elucidated the time course of DNA delivery with fluorescently labelled nanocomplex formulations in cells. It was confirmed that addition of a gadolinium lipid conjugate contrast agent allowed real time in?vivo monitoring of nanocomplex localisation in tumours by MRI, which was maintained for at least 24?h. The peptide-targeted nanocomplexes developed here allow for the specific enhancement of targeted gene therapy both in?vitro and in?vivo, whilst allowing real time monitoring of delivery with MRI.     

Incidence of and Mortality from Venous Thromboembolism in a Real-world Population: The Q-VTE Study Cohort

Background

The public health burden of venous thromboembolism, which includes deep vein thrombosis and pulmonary embolism, is not fully known, and contemporary incidence and mortality estimates are needed. We determined the incidence and case fatality of venous thromboembolism in a general population.

Methods

Using the administrative health care databases of the Canadian province of Québec, we identified all incident cases of deep vein thrombosis or pulmonary embolism between 2000 and 2009 and classified them as definite or probable venous thromboembolism. We formed 2 patient cohorts, one with definite cases and the other including cases with definite or probable venous thromboembolism that were followed until December 31, 2009.

Results

We identified 67,354 definite and 35,123 probable cases of venous thromboembolism. The age- and sex-adjusted incidence rates of definite or probable venous thromboembolism, deep vein thrombosis, and pulmonary embolism were 1.22 (95% confidence interval [CI], 1.22-1.23), 0.78 (95% CI, 0.77-0.79), and 0.45 (95% CI, 0.44-0.45) per 1000 person-years, respectively, while for definite venous thromboembolism it was 0.90 (95% CI, 0.89-0.90) per 1000 person-years. The 30-day and 1-year case-fatality rates after definite or probable venous thromboembolism were 10.6% (95% CI, 10.4-10.8) and 23.0% (95% CI, 22.8-23.3), respectively, and were slightly higher among definite cases. The 1-year survival rate was 0.47 (95% CI, 0.46-0.48) for cases with definite or probable venous thromboembolism and cancer, 0.93 (95% CI, 0.93-0.94) for cases with unprovoked venous thromboembolism, and 0.84 (95% CI, 0.83-0.84) for cases with venous thromboembolism secondary to a major risk factor. Similar survival rates were seen for cases with definite venous thromboembolism.

Conclusion

The risk of venous thromboembolism in the general population remains high, and mortality, especially in cancer patients with venous thromboembolism, is substantial.