Transcutaneous immunization with novel lipid-based adjuvants induces protection against gastric Helicobacter pylori infection

The development of vaccines to combat pathogens that infect across mucosal surfaces has been a major goal of vaccine research. Successful mucosal vaccination requires the co-administration of adjuvants that can overcome the state of immune tolerance normally associated with mucosal application of proteins. In the case of oral immunization, delivery systems are also required to protect vaccine antigens against destruction by gastric pH and digestive enzymes. Furthermore, adjuvants used for mucosal delivery must be free of neurotoxic effects like those induced by the commonly used experimental mucosal adjuvant cholera toxin. Maintenance of the "cold chain" is also essential for the effectiveness of any vaccine and adjuvants/delivery systems that enhance the stability of a vaccine would offer a significant advantage. Needle-free methods of vaccination that induce protective immunity at multiple mucosal surfaces are also desirable for rapid vaccination of large populations. In the present study we show that transcutaneous immunization (TCI) using Lipid C, a novel lipid-based matrix originally developed for oral immunization, containing soluble Helicobacter sonicate significantly reduces the gastric bacterial burden in mice following gastric challenge with live Helicobacter pylori. Protection is associated with the production of splenic gamma interferon and gastric IgA and was achieved without the co-administration of potent and potentially toxic adjuvants, although protection was further enhanced by inclusion of CpG-ODN and cholera toxin in the lipid delivery system.

A pilot study assessing the feasibility of a home-based progressive resistance exercise program and trend toward healing rates for patients with venous leg ulcers

Venous leg ulceration is a serious condition affecting 1 – 3% of the population. Decline in the function of the calf muscle pump is correlated with venous ulceration. Many previous studies have reported an improvement in the function of the calf muscle pump, endurance of the calf muscle and increased range of ankle motion after structured exercise programs. However, there is a paucity of published research that assesses if these improvements result in an improvement in the healing rates of venous ulcers. The primary purpose of this pilot study was to establish the feasibility of a homebased progressive resistance exercise program and examine if there was any clinical significance or trend toward healing. The secondary aims were to examine the benefit of a home-based progressive resistance exercise program on calf muscle pump function and physical parameters. The methodology used was a randomised controlled trial where eleven participants were randomised into an intervention (n = 6) or control group (n = 5). Participants who were randomised to receive a 12-week home-based progressive resistance exercise program were instructed through weekly face-to-face consultations during their wound clinic appointment by the author. Control group participants received standard wound care and compression therapy. Changes in ulcer parameters were measured fortnightly at the clinic (number healed at 12 weeks, percentage change in area and pressure ulcer score healing score). An air plethysmography test was performed at baseline and following the 12 weeks of training to determine changes in calf muscle pump function. Functional measures included maximum number of heel raises (endurance), maximal isometric plantar flexion (strength) and range of ankle motion (ROAM); these tests were conducted at baseline, week 6 and week 12. The sample for the study was drawn from the Princess Alexandra Hospital in Brisbane, Australia. Participants with venous leg ulceration who met the inclusion criteria were recruited. The participants were screened via duplex scanning and ankle brachial pressure index (ABPI) to ensure they did not have any arterial complications. Participants were excluded if there was evidence of cellulitis. Demographic data were obtained from each participant and details regarding medical history, quality of life and geriatric depression scores were collected at baseline. Both the intervention and control group were required to complete a weekly exercise diary to monitor activity levels between groups. To test for the effect of the intervention over time, a repeated measures analysis of variance was conducted on the major outcome variables. Group (intervention versus control) was the between subject factor and time (baseline, week 6, week 12) was the within subject or repeated measures factor. Due to the small sample size, further tests were conducted to check the assumptions of the statistical test to be used. The results showed that Mauchly.s Test, the Sphericity assumptions of repeated measures for ANOVA were met. Further tests of homogeneity of variance assumptions also confirmed that this assumption was met. Data analysis was conducted using the software package SPSS for Windows Release 17.0. The pilot study proved feasible with all of the intervention (n=6) participants continuing with the resistance program for the 12 week duration and no deleterious effects noted. Clinical significance was observed in the intervention group with a 32% greater change in ulcer size (p= 0.26) than the control group, and a 10% (p = 0.74) greater difference between the numbers healed compared to the control group. Statistical significance was observed for the ejection fraction (p = 0.05), residual volume fraction (p = 0.04) and ROAM (p = 0.01), which all improved significantly in the intervention group over time. These results are encouraging, nevertheless, further investigations seem warranted to examine the effect exercise has on the healing rates of venous leg ulcers, with a multistudy site, larger sample size and longer follow up period.

The effects of weight loss strategies on gastric emptying and appetite control

The gastrointestinal tract plays an important role in the improved appetite control and weight loss in response to bariatric surgery. Other strategies which similarly alter gastrointestinal responses to food intake could contribute to successful weight management. The aim of this review is to discuss the effects of surgical, pharmacological and behavioural weight loss interventions on gastrointestinal targets of appetite control, including gastric emptying. Gastrointestinal peptides are also discussed because of their integrative relationship in appetite control. This review shows that different strategies exert diverse effects and there is no consensus on the optimal strategy for manipulating gastric emptying to improve appetite control. Emerging evidence from surgical procedures (e.g., sleeve gastrectomy and Roux en-Y gastric bypass) suggests a faster emptying rate and earlier delivery of nutrients to the distal small intestine may improve appetite control. Energy restriction slows gastric emptying, while the effect of exercise-induced weight loss on gastric emptying remains to be established. The limited evidence suggests that chronic exercise is associated with faster gastric emptying which we hypothesise will impact on appetite control and energy balance. Understanding how behavioural weight loss interventions (e.g., diet and exercise) alter gastrointestinal targets of appetite control may be important to improve their success in weight management.

Leg Clubs - Beyond the ulcers : case studies based on participatory action research

Based on Participatory Action Research (PAR), the case studies in this paper examine the psychosocial benefits and outcomes for clients of community based Leg Clubs. The Leg Club model was developed in the United Kingdom (UK) to address the issue of social isolation and non-compliance to leg ulcer treatment. Principles underpinning the Leg Club are based on the Participatory Action Framework (PAR) where the input and involvement of participants is central. This study identifies the strengths of the Leg Club in enabling and empowering people to improve the social context in which they function. In addition it highlights the potential of expanding operations that are normally clinically based (particularly in relation to chronic conditions) but transferable to community settings in order that that they become “agents of change” for addressing such issues as social isolation and the accompanying challenges that these present, including no-compliance to treatment.

The effectiveness of a four layer compression bandage system in comparison to Class 3 compression hosiery on healing and quality of life for patients with venous leg ulcers : a randomised controlled trial

There are an increasing number of compression systems available for treatment of venous leg ulcers and limited evidence on the relative effectiveness of these systems. The purpose of this study was to conduct a randomised controlled trial to compare the effectiveness of a 4-layer compression bandage system with Class 3 compression hosiery on healing and quality of life in patients with venous leg ulcers. Data were collected from 103 participants on demographics, health, ulcer status, treatments, pain, depression and quality of life for 24 weeks. After 24 weeks, 86% of the 4-layer bandage group and 77% of the hosiery group were healed (p=0.24). Median time to healing for the bandage group was 10 weeks, in comparison to 14 weeks for the hosiery group (p=0.018). Cox proportional hazards regression found participants in the 4-layer system were 2.1 times (95% CI 1.2–3.5) more likely to heal than those in hosiery, while longer ulcer duration, larger ulcer area and higher depression scores significantly delayed healing. No differences between groups were found in quality of life or pain measures. Findings indicate these systems were equally effective in healing patients by 24 weeks, however a 4-layer system may produce a more rapid response.

Understanding the relationships between the calf muscle pump, ankle range of motion and healing for adults with venous leg ulcers: a review of the literature

Exercise offers the potential to improve circulation, wound healing outcomes, and functional and emotional wellbeing for adults experiencing venous leg ulceration. Individuals with chronic leg ulcers typically have multiple comorbidities such as arthritis, asthma, chronic obstructive airways disease, cardiac disease or neuromuscular disorders, which would also benefit from regular exercise. The aim of this review is to highlight the relationships between the calf muscle pump and venous return and range of ankle motion for adults with venous leg ulcers. The effect of exercise will also be considered in relation to the healing rates for adults experiencing venous leg ulceration. The findings suggest there is evidence that exercises which engage the calf muscle pump improve venous return. Ankle range of motion, which is crucial for complete activation of the calf muscle pump, can also be improved with simple, home-based exercise programs. However, observational studies still report that venous leg ulcer patients are less physically active than age-matched controls. Therefore, the behavioural reasons for not exercising must be considered. Only two studies, both underpowered, have assessed the effect of exercise on the healing rates of venous leg ulcers. In conclusion, exercise is feasible with this patient population. However, future studies with larger sample sizes are needed to provide stronger evidence to support the therapeutic benefit of exercise as an adjunct therapy in wound care.

National Institute for Clinical Studies Report for Phase 1, Evidence Uptake Network : Best Practice Community Care for Clients with Chronic Venous Leg Ulcers

Chronic leg ulcers cause significant pain, cost, decreased quality of life and morbidity for a considerable segment of the older population (Graham et al., 2003a). At any given time the prevalence of patients with open leg ulcers receiving treatment is between 0.11% - 0.18% (Briggs & Closs 2003). Chronic leg ulcers occur in approximately 1 - 2% of the over 60 population in the US, UK, Europe and Australia (Baker & Stacey 1994; Johnson 1995; Lees & Lambert 1992; Margolis et al. 2002). Considerable research has been undertaken to determine the best treatment practices that will aid in the management and the healing of these ulcers, and practical and effective strategies and techniques for healing venous leg ulcers have been trialled to demonstrate their beneficial effects (Nelson et al. 2004; Cullum et al. 2001)...

Does the use of store-and-forward telehealth systems improve outcomes for clinicians managing diabetic foot ulcers? : A pilot study

Diabetic foot ulcers are one of the most hospitalised diabetes complications and contribute to many leg amputations. Trained diabetic foot teams and specialists managing diabetic foot ulcers have demonstrated reductions in amputations and hospitalisation by up to 90%. Few such teams exist in Australia. Thus, access is limited for all geographical populations and may somewhat explain the high rates of hospitalisation. Aim: This pilot study aims to analyse if local clinicians managing diabetic foot complications report improved access to diabetic foot specialists and outcomes with the introduction of a telehealth store-and-forward system. Method: A store-and-forward telehealth system was implemented in six different Queensland locations between August 2009 and February 2010. Sites were offered ad hoc and/or fortnightly telehealth access to a diabetic foot speciality service. A survey was sent six months following commencement of the trial to the 14 eligible clinicians involved in the trial to gauge clinical perception of the telehealth system. Results: Eight participants returned the surveys. The majority of responding clinicians reported that the telehealth system was easy to use (100%), improved their access to diabetic foot speciality services (75%), improved upskilling of local diabetes service staff (100%), and improved patient outcomes (100%). Conclusion: This pilot study suggests that clinicians found the use of a telehealth store-and-forward system very useful in improving access to speciality services, clinical skills and patient outcomes. This study supports the recommendation that telehealth systems should be made available for diabetic foot ulcer management.

A home-based progressive resistance exercise programme for patients with venous leg ulcers : a feasibility study

This study aimed to assess the feasibility of a home-based exercise program and examine the effects on the healing rates of venous leg ulcers. A 12 –week randomised controlled trial was conducted investigating the effects of an exercise intervention compared to a usual care group. Participants in both groups (n = 13) had active venous ulceration and were treated in a metropolitan hospital outpatients clinic in Australia. Data were collected on recruitment from medical records, clinical assessment and questionnaires. Follow-up data on progress in healing and treatments were collected fortnightly for 12 weeks. Calf muscle pump function data were collected at baseline and 12 weeks from recruitment. Range of ankle motion data were collected at baseline, 6 and 12 weeks from recruitment. This pilot study indicated that the intervention was feasible. Clinical significance was observed in the intervention group with a 32% greater decrease in ulcer size (p=0.34) than the control group, and a 10% (p=0.74) improvement in the number of participants healed in the intervention group compared to the control group. Significant differences between groups over time were observed in calf muscle pump function parameters; (ejection fraction [p = 0.05]; residual volume fraction [p = 0.04]) and range of ankle motion (p = 0.01). This pilot study is one of the first studies to examine and measure clinical healing rates for participants involved in a home-based progressive resistance exercise program. Further research is warranted with a larger multi-site study.

Health service pathways for patients with chronic leg ulcers : identifying effective pathways for facilitation of evidence based wound care

Background: Chronic leg ulcers cause long term ill-health for older adults and the condition places a significant burden on health service resources. Although evidence on effective management of the condition is available, a significant evidence-practice gap is known to exist, with many suggested reasons e.g. multiple care providers, costs of care and treatments. This study aimed to identify effective health service pathways of care which facilitated evidence-based management of chronic leg ulcers. Methods: A sample of 70 patients presenting with a lower limb leg or foot ulcer at specialist wound clinics in Queensland, Australia were recruited for an observational study and survey. Retrospective data were collected on demographics, health, medical history, treatments, costs and health service pathways in the previous 12 months. Prospective data were collected on health service pathways, pain, functional ability, quality of life, treatments, wound healing and recurrence outcomes for 24 weeks from admission. Results: Retrospective data indicated that evidence based guidelines were poorly implemented prior to admission to the study, e.g. only 31% of participants with a lower limb ulcer had an ABPI or duplex assessment in the previous 12 months. On average, participants accessed care 2–3 times/week for 17 weeks from multiple health service providers in the twelve months before admission to the study clinics. Following admission to specialist wound clinics, participants accessed care on average once per week for 12 weeks from a smaller range of providers. The median ulcer duration on admission to the study was 22 weeks (range 2–728 weeks). Following admission to wound clinics, implementation of key indicators of evidence based care increased (p<0.001) and Kaplan-Meier survival analysis found the median time to healing was 12 weeks (95% CI 9.3–14.7). Implementation of evidence based care was significantly related to improved healing outcomes (p<0.001). Conclusions: This study highlights the complexities involved in accessing expertise and evidence based wound care for adults with chronic leg or foot ulcers. Results demonstrate that access to wound management expertise can promote streamlined health services and evidence based wound care, leading to efficient use of health resources and improved health.

A prospective window into medical device-related pressure ulcers in intensive care

Objective: To determine the prevalence, severity, location, etiology, treatment, and healing of medical device-related pressure ulcers in intensive care patients for up to 7 days. Design: Prospective repeated measures study. Setting and participants: Patients in 6 intensive care units of 2 major medical centers, one each in Australia and the United States, were screened 1 day per month for 6 months. Those with device-related ulcers were followed daily up to 7 days. Outcome measures: Device-related ulcer prevalence, pain, infection, treatment, healing. Results: 15/483 patients had device-related ulcers and 9/15 with 11 ulcers were followed beyond screening. Their mean age was 60.5 years, most were men, over-weight, and at increased pressure ulcer risk. Endotracheal and nasogastric tubes were the cause of most device-related ulcers. Repositioning was the most frequent treatment. 4/11 ulcers healed within the 7 day observation period. Conclusion: Device-related ulcer prevalence was 3.1%, similar to that reported in the limited literature available, indicating an ongoing problem. Systematic assessment and repositioning of devices are the mainstays of care. We recommend continued prevalence determination and that nurses remain vigilant to prevent device-related ulcers, especially in patients with nasogastric and endotracheal tubes.

Pressure ulcers in the adult intensive care unit : a literature review of patient risk factors and risk assessment scales

Background: Critically ill patients are at high risk for pressure ulcer (PrU) development due to their high acuity and the invasive nature of the multiple interventions and therapies they receive. With reported incidence rates of PrU development in the adult critical care population as high as 56%, the identification of patients at high risk of PrU development is essential. This paper will explore the association between PrU development and risk factors. It will also explore PrU development and the use of risk assessment scales for critically ill patients in adult intensive care units. Method: A literature search from 2000 to 2012 using the CINHAL, Cochrane Library, EBSCOHost, Medline (via EBSCOHost), PubMed, ProQuest and Google Scholar databases was conducted. Key words used were: pressure ulcer/s; pressure sore/s; decubitus ulcer/s; bed sore/s; critical care; intensive care; critical illness; prevalence; incidence; prevention; management; risk factor; risk assessment scale. Results: Nineteen articles were included in this review; eight studies addressing PrU risk factors, eight studies addressing risk assessment scales and three studies overlapping both. Results from the studies reviewed identified 28 intrinsic and extrinsic risk factors which may lead to PrU development. Development of a risk factor prediction model in this patient population, although beneficial, appears problematic due to many issues such as diverse diagnoses and subsequent patient needs. Additionally, several risk assessment instruments have been developed for early screening of patients at higher risk of developing PrU in the ICU. No existing risk assessment scales are valid for identification high risk critically ill patient,with the majority of scales potentially over-predicting patients at risk for PrU development. Conclusion: Research studies to inform the risk factors for potential pressure ulcer development are inconsistent. Additionally, there is no consistent or clear evidence which demonstrates any scale to better or more effective than another when used to identify the patients at risk for PrU development. Furthermore robust research is needed to identify the risk factors and develop valid scales for measuring the risk of PrU development in ICU.