A new future for growth factor complexes as wound therapies?

Background: Topical administration of growth factors (GFs) has displayed some potential in wound healing, but variable efficacy, high doses and costs have hampered their implementation. Moreover, this approach ignores the fact that wound repair is driven by interactions between multiple GFs and extracellular matrix (ECM) proteins. The Problem: Deep dermal partial thickness burn (DDPTB) injuries are the most common burn presentation to pediatric hospitals and also represent the most difficult burn injury to manage clinically. DDPTB often repair with a hypertrophic scar. Wounds that close rapidly exhibit reduced scarring. Thus treatments that shorten the time taken to close DDTPB’s may coincidently reduce scarring. Basic/Clinical Science Advances: We have observed that multi-protein complexes comprised of IGF and IGF-binding proteins bound to the ECM protein vitronectin (VN) significantly enhance cellular functions relevant to wound repair in human skin keratinocytes. These responses require activation of both the IGF-1R and the VN-binding αv integrins. We have recently evaluated the wound healing potential of these GF:VN complexes in a porcine model of DDTPB injury. Clinical Care Relevance: This pilot study demonstrates that GF:VN complexes hold promise as a wound healing therapy. Enhanced healing responses were observed after treatment with nanogram doses of the GF:VN complexes in vitro and in vivo. Critically healing was achieved using substantially less GF than studies in which GFs alone have been used. Conclusion: These data suggest that coupling GFs to ECM proteins, such as VN, may ultimately prove to be an improved technique for the delivery of novel GF-based wound therapies.

Teachers’ understanding of school connectedness : implications for the development and implementation of school based injury prevention strategies

Aim: Worldwide, injury is the leading cause of death and disability for young people. Injuries among young people are commonly associated with risk taking behaviour, including violence and transport risks, which often occur in the context of alcohol use. The school environment has been identified as having a significant role in shaping adolescent behaviour. In particular, school connectedness, the degree to which adolescents feel that they belong and are accepted at school, has been shown to be an important protective factor. Strategies for increasing school connectedness may therefore be effective in reducing risk taking and associated injury. Prior to developing connectedness strategies, it is important to understand the perspectives of those in the school regarding the construct and how it is realised in the school context. The aim of this research was to understand teachers’ perspectives of school connectedness, the strategies they employ to connect with students, and their perceptions of school connectedness as a strategy for risk taking and injury prevention. Method: In depth interviews of approximately 45 minutes duration were conducted with 13 Health and PE teachers and support staff from 2 high schools in Southeast Queensland, Australia. Additionally, 6 focus group workshop discussions were held with 35 Education department employees (5-6 per group), including teachers from 15 Southeast Queensland high schools. Results: Participants were found to place strong importance on the development of connectedness among students, including those at risk for problem behaviour. Strategies used to promote connectedness included building trust, taking an interest in each student and being available to talk to, and finding something positive for students to succeed at. Teachers identified strategies as being related to decreased risk taking behavior. Teacher training on school connectedness was perceived as an important and useful inclusion in a school based injury prevention program. Conclusions: The established link between increased school connectedness and decreased problem behaviour has implications for school based strategies designed to decrease adolescent risk taking behaviour and associated injury. Targeting school connectedness as a point of intervention, in conjunction with individual attitude and behaviour change programs, may be an effective injury prevention strategy.

Modulation of dermal microvascular endithelial cell responses to growth factors and haemostatic factors in the presence of vitronectin

In order to effect permanent closure in burns patients suffering from full thickness wounds, replacing their skin via split thickness autografting, is essential. Dermal substitutes in conjunction with widely meshed split thickness autografts (+/- cultured keratinocytes) reduce scarring at the donor and recipient sites of burns patients by reducing demand for autologous skin (both surface area and thickness), without compromising dermal delivery at the wound face. Tissue engineered products such as Integra consist of a dermal template which is rapidly remodelled to form a neodermis, at which time the temporary silicone outer layer is removed and replaced with autologous split thickness skin. Whilst provision of a thick tissue engineered dermis at full thickness burn sites reduces scarring, it is hampered by delays in vascularisation which results in clinical failure. The ultimate success of any skin graft product is dependent upon a number of basic factors including adherence, haemostasis and in the case of viable tissue grafts, success is ultimately dependent upon restoration of a normal blood supply, and hence this study. Ultimately, the goal of this research is to improve the therapeutic properties of tissue replacements, through impregnation with growth factors aimed at stimulating migration and proliferation of microvascular endothelial cells into the donor tissue post grafting. For the purpose of my masters, the aim was to evaluate the responsiveness of a dermal microvascular endothelial cell line to growth factors and haemostatic factors, in the presence of the glycoprotein vitronectin. Vitronectin formed the backbone for my hypothesis and research due to its association with both epithelial and, more specifically, endothelial migration and proliferation. Early work using a platform technology referred to as VitroGro (Tissue Therapies Ltd), which is comprised of vitronectin bound BP5/IGF-1, aided keratinocyte proliferation. I hypothesised that this result would translate to another epithelium - endothelium. VitroGro had no effect on endothelial proliferation or migration. Vitronectin increases the presence of Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factor (VEGF) receptors, enhancing cell responsiveness to their respective ligands. So, although Human Microvascular Endothelial Cell line 1 (HMEC-1) VEGF receptor expression is generally low, it was hypothesised that exposure to vitronectin would up-regulate this receptor. HMEC-1 migration, but not proliferation, was enhanced by vitronectin bound VEGF, as well as vitronectin bound Epidermal Growth Factor (EGF), both of which could be used to stimulate microvascular endothelial cell migration for the purpose of transplantation. In addition to vitronectin's synergy with various growth factors, it has also been shown to play a role in haemostasis. Vitronectin binds thrombin-antithrombin III (TAT) to form a trimeric complex that takes on many of the attributes of vitronectin, such as heparin affinity, which results in its adherence to endothelium via heparan sulfate proteoglycans (HSP), followed by unaltered transcytosis through the endothelium, and ultimately its removal from the circulation. This has been documented as a mechanism designed to remove thrombin from the circulation. Equally, it could be argued that it is a mechanism for delivering vitronectin to the matrix. My results show that matrix-bound vitronectin dramatically alters the effect that conformationally altered antithrombin three (cATIII) has on proliferation of microvascular endothelial cells. cATIII stimulates HMEC-1 proliferation in the presence of matrix-bound vitronectin, as opposed to inhibiting proliferation in its absence. Binding vitronectin to tissues and organs prior to transplant, in the presence of cATIII, will have a profound effect on microvascular infiltration of the graft, by preventing occlusion of existing vessels whilst stimulating migration and proliferation of endothelium within the tissue.

Comparison of U.S., Canadian, and Australian participants' performance on the Algase Wandering Scale-Version 2 (AWS-V2)

Background Wandering represents a major problem in the management of patients with Alzheimer’s disease (AD). In this study we examined the utility of the Algase Wandering Scale (AWS), a newly developed psychometric instrument that asks caregivers to assess the likelihood of wandering behavior. Methods The AWS was administered to the caregivers of 40 AD patients and total and subscale scores were examined in relation to measures of mental and functional status, depressive symptoms and medication usage. Results AWS scores were comparable, though slightly lower, than those normative values previously published. Higher scores were associated with more severe dementia. The Negative Outcome subscale showed a significant increase in reported falls or injuries in association with anti-depressant use. Conclusions These data provide some construct validation for the AWS as a potentially useful scale to assess wandering behaviors in AD.

What factors are associated with cyclists getting injured? Correlates of cyclist injuries in Queensland

Pedal cyclists are over-represented in traffic crash injuries in Australia. This study examined correlates of cycling injuries in a sample of Queensland cyclists. Members of Bicycle Queensland (n=1976) were asked about cycling injuries as part of an online survey. They also reported demographic characteristics, reasons for cycling, years of cycling as an adult, and cycling frequency. Multivariate logistic regression modelling was used to examine the association between these variables and experiencing cycling injuries last year (yes/no). Thirty-one percent of respondents (n=617) reported at least one cycling injury. Respondents had greater likelihood of injury if they cycled more frequently, had cycled <5 years, or cycled for recreation or competition. These findings suggest that injuries are mostly likely to occur among less experienced cyclists, those cycling the most, and those cycling for sport and recreation. Injury prevention interventions should include cycle skills training along with fostering safer cycling environments.

Health impacts of floods

Introduction: Floods are the most common hazard to cause disasters and have led to extensive morbidity and mortality throughout the world. The impact of floods on the human community is related directly to the location and topography of the area, as well as human demographics and characteristics of the built environment. Objectives: The aim of this study is to identify the health impacts of disasters and the underlying causes of health impacts associated with floods. A conceptual framework is developed that may assist with the development of a rational and comprehensive approach to prevention, mitigation, and management. Methods: This study involved an extensive literature review that located >500 references, which were analyzed to identify common themes, findings, and expert views. The findings then were distilled into common themes. Results: The health impacts of floods are wide ranging, and depend on a number of factors. However, the health impacts of a particular flood are specific to the particular context. The immediate health impacts of floods include drowning, injuries, hypothermia, and animal bites. Health risks also are associated with the evacuation of patients, loss of health workers, and loss of health infrastructure including essential drugs and supplies. In the mediumterm, infected wounds, complications of injury, poisoning, poor mental health, communicable diseases, and starvation are indirect effects of flooding. In the long-term, chronic disease, disability, poor mental health, and poverty-related diseases including malnutrition are the potential legacy. Conclusions: This article proposes a structured approach to the classification of the health impacts of floods and a conceptual framework that demonstrates the relationships between floods and the direct and indirect health consequences.

Identifying large truck hot spots using crash counts and PDOEs

Large trucks are involved in a disproportionately small fraction of the total crashes but a disproportionately large fraction of fatal crashes. Large truck crashes often result in significant congestion due to their large physical dimensions and from difficulties in clearing crash scenes. Consequently, preventing large truck crashes is critical to improving highway safety and operations. This study identifies high risk sites (hot spots) for large truck crashes in Arizona and examines potential risk factors related to the design and operation of the high risk sites. High risk sites were identified using both state of the practice methods (accident reduction potential using negative binomial regression with long crash histories) and a newly proposed method using Property Damage Only Equivalents (PDOE). The hot spots identified via the count model generally exhibited low fatalities and major injuries but large minor injuries and PDOs, while the opposite trend was observed using the PDOE methodology. The hot spots based on the count model exhibited large AADTs, whereas those based on the PDOE showed relatively small AADTs but large fractions of trucks and high posted speed limits. Documented site investigations of hot spots revealed numerous potential risk factors, including weaving activities near freeway junctions and ramps, absence of acceleration lanes near on-ramps, small shoulders to accommodate large trucks, narrow lane widths, inadequate signage, and poor lighting conditions within a tunnel.

Quality of child abuse information for measurement and surveillance : linking hospital and child welfare data

National estimates of the prevalence of child abuse-related injuries are obtained from a variety of sectors including welfare, justice, and health resulting in inconsistent estimates across sectors. The International Classification of Diseases (ICD) is used as the international standard for categorising health data and aggregating data for statistical purposes, though there has been limited validation of the quality, completeness or concordance of these data with other sectors. This research study examined the quality of documentation and coding of child abuse recorded in hospital records in Queensland and the concordance of these data with child welfare records. A retrospective medical record review was used to examine the clinical documentation of over 1000 hospitalised injured children from 20 hospitals in Queensland. A data linkage methodology was used to link these records with records in the child welfare database. Cases were sampled from three sub-groups according to the presence of target ICD codes: Definite abuse, Possible abuse, unintentional injury. Less than 2% of cases coded as being unintentional were recoded after review as being possible abuse, and only 5% of cases coded as possible abuse cases were reclassified as unintentional, though there was greater variation in the classification of cases as definite abuse compared to possible abuse. Concordance of health data with child welfare data varied across patient subgroups. This study will inform the development of strategies to improve the quality, consistency and concordance of information between health and welfare agencies to ensure adequate system responses to children at risk of abuse.

A two-compartment mechanochemical model of the roles of transforming growth factor-beta and tissue tension in dermal wound healing

The repair of dermal tissue is a complex process of interconnected phenomena, where cellular, chemical and mechanical aspects all play a role, both in an autocrine and in a paracrine fashion. Recent experimental results have shown that transforming growth factor-beta (TGF-beta) and tissue mechanics play roles in regulating cell proliferation, differentiation and the production of extracellular materials. We have developed a 1D mathematical model that considers the interaction between the cellular, chemical and mechanical phenomena, allowing the combination of TGF-beta and tissue stress to inform the activation of fibroblasts to myofibroblasts. Additionally, our model incorporates the observed feature of residual stress by considering the changing zero-stress state in the formulation for effective strain. Using this model, we predict that the continued presence of TGF-beta in dermal wounds will produce contractures due to the persistence of myofibroblasts; in contrast, early elimination of TGF-beta significantly reduces the myofibroblast numbers resulting in an increase in wound size. Similar results were obtained by varying the rate at which fibroblasts differentiate to myofibroblasts and by changing the myofibroblast apoptotic rate. Taken together, the implication is that elevated levels of myofibroblasts is the key factor behind wounds healing with excessive contraction, suggesting that clinical strategies which aim to reduce the myofibroblast density may reduce the appearance of contractures.

Evaluation of on-road driving in people with hemianopia and quadrantanopia

OBJECTIVE: To examine whether some drivers with hemianopia or quadrantanopia display safe driving skills on the road compared with drivers with normal visual fields. ---------- METHOD: An occupational therapist evaluated 22 people with hemianopia, 8 with quadrantanopia, and 30 with normal vision for driving skills during naturalistic driving using six rating scales. ---------- RESULTS: Of drivers with normal vision, >90% drove flawlessly or had minor errors. Although drivers with hemianopia were more likely to receive poorer ratings for all skills, 59.1%–81.8% performed with no or minor errors. A skill commonly problematic for them was lane keeping (40.9%). Of 8 drivers with quadrantanopia, 7 (87.5%) exhibited no or minor errors. ---------- CONCLUSION: This study of people with hemianopia or quadrantanopia with no lateral spatial neglect highlights the need to provide individual opportunities for on-road driving evaluation under natural traffic conditions if a person is motivated to return to driving after brain injury.

Exploiting system fluctuations. Differential training in physical prevention and rehabilitation programs for health and exercise

Background: Traditional causal modeling of health interventions tends to be linear in nature and lacks multidisciplinarity. Consequently, strategies for exercise prescription in health maintenance are typically group based and focused on the role of a common optimal health status template toward which all individuals should aspire. ----- ----- Materials and methods: In this paper, we discuss inherent weaknesses of traditional methods and introduce an approach exercise training based on neurobiological system variability. The significance of neurobiological system variability in differential learning and training was highlighted.----- ----- Results: Our theoretical analysis revealed differential training as a method by which neurobiological system variability could be harnessed to facilitate health benefits of exercise training. It was observed that this approach emphasizes the importance of using individualized programs in rehabilitation and exercise, rather than group-based strategies to exercise prescription.----- ----- Conclusion: Research is needed on potential benefits of differential training as an approach to physical rehabilitation and exercise prescription that could counteract psychological and physical effects of disease and illness in subelite populations. For example, enhancing the complexity and variability of movement patterns in exercise prescription programs might alleviate effects of depression in nonathletic populations and physical effects of repetitive strain injuries experienced by athletes in elite and developing sport programs.

Understanding the factors influencing safe and unsafe motorcycle rider intentions

The increasing popularity of motorcycles in Australia is a significant concern as motorcycle riders represent 15% of all road fatalities and an even greater proportion of serious injuries. This study assessed the psychosocial factors influencing motorcycle riders’ intentions to perform both safe and risky riding behaviours. Using an extended theory of planned behaviour (TPB), motorcycle riders (n = 229) from Queensland, Australia were surveyed to assess their riding attitudes, subjective norm (general and specific), perceived behavioural control (PBC), group norm, self-identity, sensation seeking, and aggression, as well as their intentions, in relation to three safe (e.g., handle my motorcycle skilfully) and three risky (e.g., bend road rules to get through traffic) riding behaviours. Although there was variability in the predictors of intention across the behaviours, results revealed that safer rider intentions were most consistently predicted by PBC, while riskier intentions were predicted by attitudes and sensation seeking. The TPB was able to explain a greater proportion of the variance for intentions to perform risky behaviours. Overall, this study has provided insight into the complexity of factors contributing to rider intentions and suggests that different practical strategies need to be adopted to facilitate safer and reduce risky rider decisions.

Injuries across adolescence : an investigation using the Extended Adolescent Injury Checklist (E-AIC)

Injury is the leading cause of death among adolescents, and in many countries, accounts for more deaths than all other causes combined. Rates of death due to injury also increase dramatically across adolescence. The Australian Institute of Health and Welfare reported that, in 2005, there were 954 deaths of young Australians due to injury, which is a rate of 26 deaths per 100,000 young people. Of these deaths, 4% were adolescents aged 12-14, 17% were aged 15-17, and 80% were aged 18-24 years. Issues addressed: Injuries are the leading cause of death among adolescents. The current research examined a measure of adolescent injury in terms of whether it encompasses the diverse injury experiences of Australian adolescents, including high-risk and normative adolescents, and thus determine its utility as a tool for health promotion research. Grade 9 students from two Brisbane high schools (n=202, aged 13-14 years) and adolescents recruited from the Emergency Department waiting rooms of four Brisbane hospitals (n=98, aged 16-18 years) completed the Extended Adolescent Injury Checklist (E-AIC). The most common cause of injury among adolescents was a sports activity, followed by fights for all participants except schoolbased males, who experienced more bicycle injuries. Alcohol use was most frequently reported in association with interpersonal violence injuries. A broad variety of injuries, occurring in context of multiple risk as well as normative behaviours, were reported by adolescents in both school and ED settings, and were captured by the E-AIC. Findings suggest that the E-AIC is a useful measure that captures the injury experiences of adolescents in different contexts. The high occurrence of injuries that do not result in formal medical treatment also indicates scope for interventions to be based around lessons in first aid, while also incorporating injury prevention components.