Effect of caffeine on adenosine-induced reversible perfusion defects assessed by automated analysis

Objectives This prospective study investigated the effects of caffeine ingestion on the extent of adenosine-induced perfusion abnormalities during myocardial perfusion imaging (MPI). Methods Thirty patients with inducible perfusion abnormalities on standard (caffeine-abstinent) adenosine MPI underwent repeat testing with supplementary coffee intake. Baseline and test MPIs were assessed for stress percent defect, rest percent defect, and percent defect reversibility. Plasma levels of caffeine and metabolites were assessed on both occasions and correlated with MPI findings. Results Despite significant increases in caffeine [mean difference 3,106 μg/L (95% CI 2,460 to 3,752 μg/L; P < .001)] and metabolite concentrations over a wide range, there was no statistically significant change in stress percent defect and percent defect reversibility between the baseline and test scans. The increase in caffeine concentration between the baseline and the test phases did not affect percent defect reversibility (average change −0.003 for every 100 μg/L increase; 95% CI −0.17 to 0.16; P = .97). Conclusion There was no significant relationship between the extent of adenosine-induced coronary flow heterogeneity and the serum concentration of caffeine or its principal metabolites. Hence, the stringent requirements for prolonged abstinence from caffeine before adenosine MPI—based on limited studies—appear ill-founded.

Human Kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy donors and prostate cancer patients.

Immunotherapy is a promising new treatment for patients with advanced prostate and ovarian cancer, but its application is limited by the lack of suitable target antigens that are recognized by CD8+ cytotoxic T lymphocytes (CTL). Human kallikrein 4 (KLK4) is a member of the kallikrein family of serine proteases that is significantly overexpressed in malignant versus healthy prostate and ovarian tissue, making it an attractive target for immunotherapy. We identified a naturally processed, HLA-A*0201-restricted peptide epitope within the signal sequence region of KLK4 that induced CTL responses in vitro in most healthy donors and prostate cancer patients tested. These CTL lysed HLA-A*0201+ KLK4 + cell lines and KLK4 mRNA-transfected monocyte-derived dendritic cells. CTL specific for the HLA-A*0201-restricted KLK4 peptide were more readily expanded to a higher frequency in vitro compared to the known HLA-A*0201-restricted epitopes from prostate cancer antigens; prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP). These data demonstrate that KLK4 is an immunogenic molecule capable of inducing CTL responses and identify it as an attractive target for prostate and ovarian cancer immunotherapy.

Assessing Cardiovascular Risk in Regional Areas: The Healthy Hearts – Beyond City Limits Program

Background: Cardiovascular disease (CVD) is more prevalent in regional and remote Australia compared to metropolitan areas. The aim of Healthy Hearts was to determine age and sex specific CVD risk factor levels and the potential value of national risk clinics. Methods: Healthy Hearts was an observational research study conducted in four purposefully selected higher risk communities in regional Victoria, Australia. The main outcome measures were the proportion of participants with CVD risk factors with group comparisons to determine the adjusted likelihood of elevated risk factor levels. Trained personnel used a standardized protocol over four weeks per community to measure CVD risk factor levels, estimate absolute CVD risk and provide feedback and advice. Results: A total of 2125 self-selected participants were assessed (mean age 58 ± 15 years, 57% women). Overall, CVD risk factors were highly prevalent. More men than women had ≥ 2 modifiable CVD risk factors (76% vs. 68%, p < .001), pre-existing CVD (20 vs. 15%, p < .01) and a major ECG abnormality requiring follow-up (15% vs. 7%, p < .001) . Less men reported depressive symptoms compared to women (28% vs. 22%, p < .01). A higher proportion of women were obese (adjusted OR 1.36, 95% CI 1.13 to 1.63), and physically inactive (adjusted OR 1.32, 95% CI 1.07 to 1.63). Conclusions: High CVD risk factor levels were confirmed for regional Victoria. Close engagement with individuals and communities provides scope for the application of regional risk management clinics to reduce the burden of CVD risk in regional Australia.

Telehealth for nursing homes: the utilization of specialist services for residential care

Specialist care consultations were identified by two research nurses using documentation in patient records, appointment diaries, electronic billing services and on-site observations at a 441-bed long term care facility. Over a six-month period there were 3333 consultations (a rate of 1511 consultations per year per 100 beds). Most consultations were for general practice (n = 2589, 78%); these consultations were mainly on site (99%), with only 27 taking place off site. There were 744 consultations for specialities other than general practice. A total of 146 events related to an emergency or unplanned hospital admission. The remaining medical consultations (n = 598, 18%) related to 23 medical specialities. The largest number of consultations were for surgery (n = 106), podiatry (n = 100), nursing services including wound care (n = 74), imaging (n = 41) and ophthalmology (n = 40). Many services which are currently being provided on site to metropolitan long-term care facilities could be provided by telehealth in both urban and rural facilities.

Postpartum diet quality in Australian women following a gestational diabetes pregnancy

BACKGROUND/OBJECTIVES: To describe the diet quality of a national sample of Australian women with a recent history of gestational diabetes mellitus (GDM) and determine factors associated with adherence to national dietary recommendations. SUBJECTS/METHODS: A postpartum lifestyle survey with 1499 Australian women diagnosed with GDM p3 years previously. Diet quality was measured using the Australian recommended food score (ARFS) and weighted by demographic and diabetes management characteristics. Multinominal logistic regression analysis was used to determine the association between diet quality and demographic characteristics, health seeking behaviours and diabetes-related risk factors. RESULTS: Mean (±s.d.) ARFS was 30.9±8.1 from a possible maximum score of 74. Subscale component scores demonstrated that the nuts/legumes, grains and fruits were the most poorly scored. Factors associated with being in the highest compared with the lowest ARFS quintile included age (odds ratio (OR) 5-year increase=1.40; 95% (confidence interval) CI:1.16–1.68), tertiary education (OR=2.19; 95% CI:1.52–3.17), speaking only English (OR=1.92; 95% CI:1.19–3.08), being sufficiently physically active (OR=2.11; 95% CI:1.46–3.05), returning for postpartum blood glucose testing (OR=1.75; 95% CI:1.23–2.50) and receiving riskreduction advice from a health professional (OR=1.80; 95% CI:1.24–2.60). CONCLUSIONS: Despite an increased risk of type 2 diabetes, women in this study had an overall poor diet quality as measured by the ARFS. Women with GDM should be targeted for interventions aimed at achieving a postpartum diet consistent with the guidelines for chronic disease prevention. Encouraging women to return for follow-up and providing risk reduction advice may be positive initial steps to improve diet quality, but additional strategies need to be identified.

Appraisal of the quality of care of older people with cognitive impairment presenting to emergency departments

The medical records of 273 patients 75 years and older were reviewed to evaluate quality of emergency department (ED) care through the use of quality indicators. One hundred fifty records contained evidence of an attempt to carry out a cognitive assessment. Documented evidence of cognitive impairment (CI) was reported in 54 cases. Of these patients, 30 had no documented evidence of an acute change in cognitive function from baseline; of 26 patients discharged home with preexisting CI (i.e., no acute change from baseline), 15 had no documented evidence of previous consideration of this issue by a health care provider; and 12 of 21 discharged patients who screened positive for cognitive issues for the first time were not referred for outpatient evaluation. These findings suggest that the majority of older adults in the ED are not receiving a formal cognitive assessment, and more than half with CI do not receive quality of care according to the quality indicators for geriatric emergency care. Recommendations for improvement are discussed.

Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010 : a systematic analysis for the Global Burden of Disease Study 2010

Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient −0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. Funding Bill & Melinda Gates Foundation.

Paramedics' perceptions of their role in palliative care : analysis of focus group transcripts

Paramedics play an important role in out-of-hospital health care. They provide unscheduled care, assisting both patients with minor injuries and those experiencing life-threatening emergencies. Increasingly, paramedics are called on to manage chronic and complex health needs, including symptom relief for patients at the end of life. However, paramedics may not be well prepared to offer palliative care, as practice guidelines and education tend to focus on the management of acute medical emergencies and major trauma. Emergency medical services that employ paramedics rarely have practice guidelines or protocols that deal specifically with palliative care.

Sustainability initiatives in early years settings

Children bring much knowledge about sustainability issues into the early childhood classroom. In recent times, I have overheard children as young as three years of age discuss events such as the BP Oil Spill in American waters and extreme weather patterns. While aspects of these events can be overwhelming, responding to children's existing knowledge allows for an educative approach to sustainability issues, and a focus on the multitude of ways individuals and communities are working to create positive change.

Review article : paramedic education opportunities and challenges in Australia

Paramedic education has been undergoing major development in Australia in the past 20 years, with many different educational programmes being developed across all Australian jurisdictions. This paper aims to review the current paramedic education programmes in Australia to identify the similarities and differences between the programmes, and the strengths and challenges in these programmes. A literature search was performed using six scientific databases to identify any systematic reviews, literature reviews or relevant articles on the topic. Additional searches included journal articles and text references from 1995 to 2011. The search was conducted during December 2010 and November 2011. Included in this review are a total of 28 articles, which are focused around five major issues in paramedic education: (i) principle on paramedic programmes and the involvement of industry partners; (ii) clinical placements; (iii) contemporary methods of education; (iv) needs for specific programmes within paramedic education; and (v) articles related to the accreditation process for paramedic programmes. Paramedic programmes across Australian universities vary with many different practices, especially relating to clinical placements in the field. The further advances of the paramedic education programmes should aim to respond to population change and industry development, which would enhance the paramedic profession across Australia.

Action for change? Embedding Aboriginal and Torres Strait Islander perspectives in early childhood education curricula

This thesis focuses on non-Indigenous educators’ work around embedding Indigenous perspectives in early childhood education curricula. In place of reporting examples of ‘good’ educational practice, the study questions how whiteness and racism continue to operate in diversity work that is seen to be productive and inclusive. The thesis argues for a more comprehensive framework for embedding Indigenous perspectives in before-school contexts to support educators’ efforts. New strategies for professional development are also suggested to support changes in disciplinary knowledge and pedagogy.

Improving psychosocial care: a professional development programme

Despite the numerous reports of difficulties experienced by health care providers in providing psychosocial care to terminally ill patients and their families, few studies have yet been undertaken to examine the effectiveness of different educational approaches to addressing these issues. The aim of this paper is to describe a programme of professional development for palliative care nurses, which is currently being offered to 181 registered nurses in Queensland, Australia. The programme is based on an action learning model and is designed to facilitate processes of reflection and peer consultation. In Part One of this paper, a review of this literature is presented to provide the background and rationale for the programme design. Details of the research programme developed to evaluate the programme will be presented in Part Two of this paper, which is to be published in the next issue of this Journal. Surveys of health professionals suggest that the demands of working with terminally ill patients are associated with a great deal of stress (Beaton and Degner 1990, Seale 1992, Vachon 1995), and emotional burden, as they are confronted with their patients' physical and emotional suffering over extended periods of time (Ullrich and Fitzgerald 1990). Key areas of concern (Lyons 1988, Bramwell 1989, Seale 1992, Copp and Dunn 1993, Wilkinson 1995) include: * Handling questions and conversations with dying patients. * Dealing with ethical and moral issues. * Handling emotions. * Giving hope. * Providing spiritual care and bereavement support. * Confronting team communication problems.

New directions in intercultural early education in Australia

Early education in Australia encompasses both early education and care(ECEC) and the early years of school. Educational approaches to cultural and linguistic diversity have varied not only by sector but also by jurisdiction based on distinct curriculum frameworks and policies. In Australian early education, provision for cultural and linguistic diversity has been framed largely by multicultural discourse, as defined by a complex history of progressive, yet often superficial reforms. Current initiatives serve to change this trajectory and the positioning of stakeholders. The incorporation of intercultural rather than multicultural approaches offers new possibilities for early education and directs attention to real challenges for ECEC. They re-position Aboriginal and Torres Strait Islanders as the First Australians, and direct attention to both Australia’s social, cultural and linguistic diversity and to the role of early childhood educators in enacting more inclusive pedagogies. Challenges yet to be addressed include the cultural understanding of Australian early childhood educators, particularly those who identify as Anglo- Australian, deeper policy enactment in pedagogic practice and negotiation with diverse families and communities. This paper will address the historical and current policy contexts of intercultural early education in Australia, the development of intercultural initiatives, and emerging issues as national policies are introduced. The discussion draws on responses to intercultural early education in New Zealand and Canada to consider approaches to intercultural priorities in Australia. The paper will attend predominantly to Aboriginal and Torres Strait Islander perspectives as a core element of change in Australian early childhood policy, focusing on ECEC.

Packed red blood cells suppress myeloid dendritic cell and monocyte inflammatory responses in a whole blood model of transfusion

Purpose/Objective: The basis for poor outcomes in some patients post transfusion remains largely unknown. Despite leukodepletion, there is still evidence of immunomodulatory effects of transfusion that require further study. In addition, there is evidence that the age of blood components transfused significantly affects patient outcomes. Myeloid dendritic cell (DC) and monocyte immune function were studied utilising an in vitro whole blood model of transfusion. Materials and methods: Freshly collected (‘recipient’) whole blood was cultured with ABO compatible leukodepleted PRBC at 25% blood replacement-volume (6hrs). PRBC were assayed at [Day (D) 2, 14, 28and 42 (date-of expiry)]. In parallel, LPS or Zymosan (Zy) were added to mimic infection. Recipients were maintained for the duration of the time course (2 recipients, 4 PRBC units, n = 8).Recipient DC and monocyte intracellular cytokines and chemokines (IL-6, IL-10, IL-12,TNF-a, IL-1a, IL-8, IP-10, MIP-1a, MIP-1b, MCP-1) were measured using flow cytometry. Changes in immune response were calculated by comparison to a parallel no transfusion control (Wilcoxin matched pairs). Influence of storage age was calculated using ANOVA. Results: Significant suppression of DC and monocyte inflammatory responses were evident. DC and monocyte production of IL-1a was reduced following exposure to PRBC regardless of storage age (P < 0.05 at all time points). Storage independent PRBC mediated suppression of DC and monocyte IL-1a was also evident in cultures costimulated with Zy. In cultures co-stimulated with either LPS or Zy, significant suppression of DC and monocyte TNF-a and IL-6 was also evident. PRBC storage attenuated monocyte TNF-a production when co-cultured with LPS (P < 0.01 ANOVA). DC and monocyte production of MIP-1a was significantly reduced following exposure to PRBC (DC: P < 0.05 at D2, 28, 42; Monocyte P < 0.05 all time points). In cultures co-stimulated with LPS and zymosan, a similar suppression of MIP-1a production was also evident, and production of both DC and monocyte MIP-1b and IP-10 were also significantly reduced. Conclusions: The complexity of the transfusion context was reflected in the whole blood approach utilised. Significant suppression of these key DC and monocyte immune responses may contribute to patient outcomes, such as increased risk of infection and longer hospital stay, following blood transfusion.

Bridging the biology of the ovine TRALI model – human inflammatory cell responses to TRALI inducing supernatants

Background Transfusion-related acute lung injury (TRALI) is a serious and potentially fatal consequence of transfusion. A two-event TRALI model demonstrated date-of-expiry - day (D) 5 platelet (PLT) and D42 packed red blood cell (PRBC) supernatants (SN) induced TRALI in LPS-treated sheep. We have adapted a whole blood transfusion culture model as an investigative bridge between the ovine TRALI model human responses to transfusion. Methods A whole blood transfusion model was adapted to replicate the ovine model - specifically +/- 0.23μg/mL LPS as the first event and 10% SN volume (transfusion) as the second event. Four pooled SN from blood products, previously used in the TRALI ovine model, were investigated: D1-PLT, D5-PLT, D1-PRBC, and D42-PRBC. Fresh human whole blood (recipient) was mixed with combinations of LPS and BP-SN stimuli and incubated in vitro for 6 hrs. Addition of golgi plug enabled measurement of monocyte cytokine production (IL-6, IL-8, IL-10, IL-12, TNF-α, IL-1α, CXCL-5, IP-10, MIP-1α, MCP-1) using multi-colour flow cytometry. Responses for 6 recipients were assessed. Results In the presence of LPS, D42-PRBC-SN significantly increased monocyte IL-6 (P=0.031), IL-8 (P=0.016) and IL-1α (P=0.008) production compared to D1-PRBC-SN. This response to D42-PRBC-SN was LPS-dependent, and was not evident in non-LPSstimulated controls. This response was also specific to D42-PRBC-SN, as similar changes were not evident for the D5-PLT-SN, compared to the D1-PLT-SN, regardless of the presence of LPS. D5-PLT-SN significantly increased IL-12 production (P=0.024) compared to D1-PLT-SN. This response was again LPS-dependent. Conclusions These data demonstrate a novel two-event mechanism of monocyte inflammatory response that was dependent upon both the presence of date-of-expiry blood product SN and LPS. Further, these results demonstrate different cytokines responses induced by date-of-expiry PLT-SN and PRBC-SN. These data are consistent with the evidence from the ovine TRALI model, and enhancing its relevance to transfusion related changes in humans.