848 resultados para Drug Utilization Review


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The behaviour of cells cultured within three-dimensional (3D) structures rather than onto two-dimensional (2D) culture plastic more closely reflects their in vivo responses. Consequently, 3D culture systems are becoming crucial scientific tools in cancer cell research. We used a novel 3D culture concept to assess cell-matrix interactions implicated in carcinogenesis: a synthetic hydrogel matrix equipped with key biomimetic features, namely incorporated cell integrin-binding motifs (e.g. RGD peptides) and the ability of being degraded by cell-secreted proteases (e.g. matrix metalloproteases). As a cell model, we chose epithelial ovarian cancer, an aggressive disease typically diagnosed at an advanced stage when chemoresistance occurs. Both cell lines used (OV-MZ-6, SKOV-3) proliferated similarly in 2D, but not in 3D. Spheroid formation was observed exclusively in 3D when cells were embedded within hydrogels. By exploiting the design flexibility of the hydrogel characteristics, we showed that proliferation in 3D was dependent on cell-integrin engagement and the ability of cells to proteolytically remodel their extracellular microenvironment. Higher survival rates after exposure to the anti-cancer drug paclitaxel were observed in cell spheroids grown in hydrogels (40-60%) compared to cell monolayers in 2D (20%). Thus, 2D evaluation of chemosensitivity may not reflect pathophysiological events seen in patients. Because of the design flexibility of their characteristics and their stability in long-term cultures (28 days), these biomimetic hydrogels represent alternative culture systems for the increasing demand in cancer research for more versatile, physiologically relevant and reproducible 3D matrices.

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This study investigated a novel drug delivery system (DDS), consisting of polycaprolactone (PCL) or polycaprolactone 20% tricalcium phosphate (PCL-TCP) biodegradable scaffolds, fibrin Tisseel sealant and recombinant bone morphogenetic protein-2 (rhBMP-2) for bone regeneration. PCL and PCL-TCP-fibrin composites displayed a loading efficiency of 70% and 43%, respectively. Fluorescence and scanning electron microscopy revealed sparse clumps of rhBMP-2 particles, non-uniformly distributed on the rods’ surface of PCL-fibrin composites. In contrast, individual rhBMP-2 particles were evident and uniformly distributed on the rods’ surface of the PCL-TCP-fibrin composites. PCL-fibrin composites loaded with 10 and 20 μg/ml rhBMP-2 demonstrated a triphasic release profile as quantified by an enzyme-linked immunosorbent assay (ELISA). This consisted of burst releases at 2 h, and days 7 and 16. A biphasic release profile was observed for PCL-TCP-fibrin composites loaded with 10 μg/ml rhBMP-2, consisting of burst releases at 2 h and day 14. PCL-TCP-fibrin composites loaded with 20 μg/ml rhBMP-2 showed a tri-phasic release profile, consisting of burst releases at 2 h, and days 10 and 21. We conclude that the addition of TCP caused a delay in rhBMP-2 release. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and alkaline phosphatase assay verified the stability and bioactivity of eluted rhBMP-2 at all time points

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This paper reviews the main studies on transit users’ route choice in thecontext of transit assignment. The studies are categorized into three groups: static transit assignment, within-day dynamic transit assignment, and emerging approaches. The motivations and behavioural assumptions of these approaches are re-examined. The first group includes shortest-path heuristics in all-or-nothing assignment, random utility maximization route-choice models in stochastic assignment, and user equilibrium based assignment. The second group covers within-day dynamics in transit users’ route choice, transit network formulations, and dynamic transit assignment. The third group introduces the emerging studies on behavioural complexities, day-to-day dynamics, and real-time dynamics in transit users’ route choice. Future research directions are also discussed.

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This review evaluated the strength of the evidence for a causal relationship between physical activity (PA) and colorectal cancer (CRC). A systematic review of databases through February 2008 was conducted to identify studies that assessed the association between total or recreational PA and incidence or mortality of CRC (including CRC, rectal cancer, colon cancer, and proximal or distal colon cancer). Studies were evaluated for significant associations between PA and risk of CRC endpoints and for evidence of dose–response relationships in the highest quality studies. Twenty cohort studies were evaluated; 11 were high-quality. Fifty percent of all studies and 64%of highest quality studies reported at least one significant association between PA and risk of a CRC endpoint (Po0.05).However, only 28%of all analyses (31% of analyses of highest quality studies) were significant (Po0.05). Only 40% of analyses of highest quality studies resulted in a significant P for trend (Po0.05); however, a non-significant inverse linear association between PA and colon cancer riskwas apparent.Heterogeneity in the evidence from all studies and from the highest quality studies was evident. Evidence from cohort studies is not sufficient to claim a convincing relationship exists between PA and CRC risk.

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Introduction: Cancer is increasingly being viewed as a chronic illness requiring long-term management, and there is a growing need for evidence-based rehabilitation interventions for cancer survivors. Previous reviews have evaluated the benefits of exercise interventions for patients undergoing cancer treatment and long-term survivors, but none have investigated the role of exercise during cancer rehabilitation, the period immediately following cancer treatment completion. This systematic review summarises the literature on the health effects of exercise during cancer rehabilitation and evaluates the methodological rigour of studies in this area to date.----------- Methods: Relevant studies were identified through a systematic search of PubMed and Embase to April 2009. Data on study design, recruitment strategy, participants, exercise intervention, adherence rates, and outcomes were extracted. Methodological rigour was assessed using a structured rating system.---------- Results: Ten studies were included. Breast cancer patients were the predominate patient group represented. Most interventions were aerobic or resistance-training exercise programmes, and exercise type, frequency, duration and intensity varied across studies. Improvements in physical functioning, strength, physical activity levels, quality of life, fatigue, immune function, haemoglobin concentrations, potential markers of recurrence, and body composition were reported. However, all studies were limited by incomplete reporting and methodological limitations.---------- Conclusions: Although the methodological limitations of studies in this new field must be acknowledged, initial evidence indicates that exercise is feasible and may provide physiological and psychological benefits for cancer survivors during the rehabilitation period. Future studies with rigorous study designs are now required to advance the field.

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Although rarely referred to in litigation in the years that have followed the Ipp Review Report, there may well be some merit in more frequent judicial reference to the NHMRC guidelines for medical practitioners on providing information to patients 2004.

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Aim: There has been no systematic research on the role of cooking skills for improving dietary intakes in Australia. Cooking skills are proposed to be declining and/or being devalued. If cooking skills have been devalued and declining, then what evidence is there for this decline and what impact might this have on dietary intakes? The aim of the present paper is to explore these assumptions with particular reference to Australia. The objectives of the present paper are to define the terms cooking and cooking skills, discuss evidence on levels of cooking skills in Australia and describe the evidence linking cooking skills to dietary intakes.---------- Methods: A review of the peer-reviewed literature using multiple databases from 1990 to September 2009.---------- Results: Cooking skills are complex and require a range of processes for people to develop efficiency or confidence in food preparation. There is little evidence on the level of cooking skills in the Australian population and how this relates to dietary intakes. The Australian Bureau of Statistic’s latest Time Use Survey and Household Expenditure Survey suggest that cooking is still a gendered activity and that the time devoted to cooking has changed little in the past 15 years, but there is an increasing use of foods prepared outside the home.---------- Conclusion: Further research is required to examine the prevalence of different types and levels of cooking skills in Australia as well as their potential effects on dietary intakes. Dietitians need evidence about the level of cooking skills people require for healthy dietary intakes.

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Background: Acute coronary syndromes are a major cause of mortality and morbidity. Objectives/Methods: The objective of this evaluation is to review the clinical trials of two new drugs being developed for the treatment of acute coronary syndromes. The first drug is the anti-coagulant otamixaban, and the trial compared otamixaban with unfractionated heparin and eptifibatide in acute coronary syndromes. The second drug is the anti-platelet ticagrelor, and the trial compared ticagrelor with clopidogrel in acute coronary syndromes. Results: In the SEPIA-ACS1 TIMI 42 trial, the primary efficacy endpoint occurred in 6.2% of subjects treated with unfractionated heparin and eptifibatide, and to a significantly lesser extent with otamixaban. In the PLATO trial, the primary efficacy endpoint had occurred less in the ticagrelor group (9.8%) than in the clopidogrel group (11.7%) at 12 months. Conclusions: Two new drugs for acute coronary syndromes, otamixaban and ticagrelor, have recently been shown to have benefits in subjects undergoing percutaneous interventions compared to the present standard regimens for this condition.

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With an increasing level of collaboration amongst researchers, software developers and industry practitioners in the past three decades, building information modelling (BIM) is now recognized as an emerging technological and procedural shift within the architect, engineering and construction (AEC) industry. BIM is not only considered as a way to make a profound impact on the professions of AEC, but is also regarded as an approach to assist the industry to develop new ways of thinking and practice. Despite the widespread development and recognition of BIM, a succinct and systematic review of the existing BIM research and achievement is scarce. It is also necessary to take stock on existing applications and have a fresh look at where BIM should be heading and how it can benefit from the advances being made. This paper first presents a review of BIM research and achievement in AEC industry. A number of suggestions are then made for future research in BIM. This paper maintains that the value of BIM during design and construction phases is well documented over the last decade, and new research needs to expand the level of development and analysis from design/build stage to postconstruction and facility asset management. New research in BIM could also move beyond the traditional building type to managing the broader range of facilities and built assets and providing preventative maintenance schedules for sustainable and intelligent buildings

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The efficacy of road safety countermeasures to deter motorists from engaging in illegal behaviours is extremely important when considering the personal and economic impact of road accidents on the community. Within many countries, deterrence theory has remained a cornerstone to criminology and criminal justice policy, particularly within the field of road safety, as policy makers and enforcement agencies attempt to increase perceptions regarding the certainty, severity and swiftness of sanctions for those who engage in illegal motoring behaviours. Using the Australian experience (particularly the tremendous amount of research into drink driving), the current paper reviews the principles underpinning deterrence theory, the utilisation of the approach within some contemporary road safety initiatives (e.g., Random Breath Testing) as well as highlights some methods to enhance a deterrent effect. The paper also provides direction for future deterrence-based research, in particular, considering the powerful impact of non-legal sanctions, punishment avoidance as well as creating culturally embedded behavioural change.

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This research uses confirmatory factor analysis and structural equation modelling to examine how organizational size - made up of four dimensions - control, resources, trust and complexity - impacts on utilization of industry-led supply chain innovation capacity in a traditional agribusiness industry, the Australian beef industry. It confirms small business rather than larger business accords greater importance to exploiting supply chain dynamic capabilities, particularly in relation to utilizing industry –led supply chain innovation capacity. For small business in Australian beef supply chains, being agile and able to adapt and align their business practices with supply chain partners is integral to ensuring these businesses remain relevant and competitive in this market. In theoretical terms this is supported by authors in the dynamic capabilities literature as they argue these types of capabilities enable organizations to innovate faster (or better), often leading to the creation of newer sources of competitive advantage.

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Report for City Design, for Environment and Parks, within the Brisbane City Council. Context of this Project A Conservation Study for the Old Brisbane Botanic Gardens, formerly called the Brisbane City Botanic Gardens, was finalised in 1995 and prepared by Jeannie Sim for the Landscape Section of Brisbane City Council, the same author of the present report. This unpublished report was the first conservation plan prepared for the place and it was recommended that it be reviewed in five years time. That time has arrived finally with the preparation of the 2005 Review. The present project was commissioned by City Design on behalf of Environment and Parks Section of Brisbane City Council. The author has purposely chosen to call the study site the 'Old Brisbane Botanic Gardens' (OBBG) to differentiate it from the Brisbane Botanic Gardens, Mt. Coot-tha (BBG-MC), and to maintain the claim for this original garden to remain as a botanic garden for Brisbane. This name immediately brings to mind an association with history, as in the precedent set by the naming of the nearby 'Old Government House' at Gardens Point.

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In many countries, the main providers for major infrastructure projects are government or public agencies. Public infrastructure projects includes economic and social infrastructure such as transportation, education and health facilities. Most decision-making models for delivery of public infrastructure projects are heavily weighted towards financial/economic factors. In Australia, public participation is an essential instrument in the procurement of infrastructure and development within Australia. This study reviews the public participation, values and interests in the procurement of infrastructure projects in Australia, and identifies the research direction in this research area in order to improve the decision-making models that capture stakeholder social, economical and environmental concerns in infrastructure projects.

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The detached housing scheme is a unique and exclusive segment of the residential property market in Malaysia. Generally, the product is expensive and for many Malaysians who can afford them, owning a detached house is a once in a lifetime opportunity. In spite of this, most of the owners fail to fully comprehend the specific need of this type of housing scheme, increasing the risk of it being a problematic project. Unlike other types of pre-designed ‘mass housing’ schemes, the detached housing scheme may be built specifically to cater the needs and demands of its owner. Therefore, maximum owner participation is vital as the development progresses to guarantee the success of the project. In addition, due to it’s unique design the house would have to individually comply with the requirements and regulations of relevant authorities. Failure of owner to recognise this will result in delays, fines and penalties, disputes and ultimately cost overruns. These circumstances highlight the need for a model to guide the owner through the entire development process of a detached house. Therefore, this research aims to develop a model for a successful detached housing development in Malaysia through maximising owner participation during it’s various development stages. To achieve this, questionnaire surveys and case studies methods shall be employed to acquire the detached housing owners’ experiences in developing their detached houses in Malaysia. Relevant statistical tools shall be applied to analyse the responses. The results gained from this study shall be synthesised into a model of successful detached housing development for the reference of future detached housing owners in Malaysia.