Indications, durations and outcomes of mechanical ventilation in dogs and cats with tick paralysis caused by Ixodes holocyclus: 61 cases (2008-2011)

Objectives: The primary objectives of this research were to describe the indications for mechanical ventilation, the duration of mechanical ventilation and probability of survival in dogs and cats with respiratory failure induced by the Australian paralysis tick (Ixodes holocyclus). Methods: A retrospective case series and a retrospective single cohort study were conducted using dogs and cats with tick paralysis requiring mechanical ventilation. An index of oxygenating performance of the lung (PF ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen) was derived from arterial blood gas analysis; patients euthanased because of veterinary costs were identified and Kaplan-Meier survival analyses performed. Results: In total, 36.6% of patients were ventilated because of hypoxaemia refractory to oxygen therapy, 38.3% because of hypoventilation, 18.3% because of unsustainable respiratory effort and 6.6% because of respiratory arrest. Median duration of mechanical ventilation was 23h, median time hospitalised was 84h and 63.9% of all patients requiring mechanical ventilation survived to discharge from the hospital. Survival probability increased to 75% when cases of cost-based euthanasia were right-censored rather than treated as deaths. The survival probability of patients ventilated because of hypoxaemia (52.6%) was significantly less than for those ventilated because of hypoventilation (90.5%). The first measured PF ratio after commencing mechanical ventilation was not significantly associated with survival probability. Conclusions: Dogs and cats with tick paralysis requiring mechanical ventilation to manage respiratory failure have reasonable survival probability. Dogs and cats requiring mechanical ventilation because of hypoventilation have a higher survival probability than those with oxygenation failure

Modelling the impact, costs and benefits of falls prevention measures to support policy-makers and program planners

The ageing of the population is one of the major transformations being experienced in Australia, with falls a significant threat to safety, health and independence. There is now substantial evidence regarding effective interventions for preventing falls among older people living independently in the community. The aim of this project was to develop and apply a framework for epidemiological modelling of the population level impact of proven interventions on future fall rates, providing a powerful policy-setting tool for prevention. We used the Cochrane review to source current best efficacy evidence from randomised controlled trials which have provided evidence of minimising the incidence of falls among older people living in the community. Six interventions defined in that review as most promising for community dwelling older people were modelled. Additionally, one other intervention not in the Cochrane review, expedited cataract removal, was also modelled. Occupational therapy delivered home hazard assessment and modification for those with recent fall history, as modelled here, represents the best falls prevention investment. Cardiac pacing is a good falls prevention investment over the medium term, although is unlikely to have a major impact on population level hospital admission rates. The relative cost-effectiveness of psychotropic medication withdrawal appears high, although some implementation issues would need to be addressed and further costs included. Multi-disciplinary multi-factorial risk management represents good clinical practice for high risk individuals, but is not relatively cost-effective for widespread implementation. Tai chi programs may represent good value for falls prevention resources, if local circumstances allow the cost per participant to be substantially lower than modelled here. Predicted reductions in national fall-related hospital admission rates for people aged 65 years and over ranged from 0.4% to 4.6% for five of the six falls prevention strategies implemented over a one year period. These reductions, however, suggest that substantial investment in falls prevention will be required to have large effects on the fall-related hospitalisation rates. In addition, the costeffectiveness of a number of the modelled interventions could be improved by variations to the implementation processes such as measures to increase uptake, or decrease the cost per participant. The framework developed provides the potential for the research evidence base to better guide policy and practice with respect to reducing falls and future fall-related hospitalisation rates

Defining the role of DAG, mitochondrial function, and lipid deposition in palmitate-induced proinflammatory signaling and its counter-modulation by palmitoleate

Chronic exposure of skeletal muscle to saturated fatty acids, such as palmitate (C16:0), enhances proinflammatory IKK-NFκB signaling by a mechanism involving the MAP kinase (Raf-MEK-ERK) pathway. Raf activation can be induced by its dissociation from the Raf-kinase inhibitor protein (RKIP) by diacylglycerol (DAG)-sensitive protein kinase C (PKC). However, whether these molecules mediate the proinflammatory action of palmitate, an important precursor for DAG synthesis, is currently unknown. Here, involvement of DAG-sensitive PKCs, RKIP, and the structurally related monounsaturated fatty acid palmitoleate (C16:1) on proinflammatory signaling are investigated. Palmitate, but not palmitoleate, induced phosphorylation/activation of the MEK-ERK-IKK axis and proinflammatory cytokine (IL-6, CINC-1) expression. Palmitate increased intramyocellular DAG and invoked PKC-dependent RKIP(Ser153) phosphorylation, resulting in RKIP-Raf1 dissociation and MEK-ERK signaling. These responses were mimicked by PMA, a DAG mimetic and PKC activator. However, while pharmacological inhibition of PKC suppressed PMA-induced activation of MEK-ERK-IKK signaling, activation by palmitate was upheld, suggesting that DAG-sensitive PKC and RKIP were dispensable for palmitate's proinflammatory action. Strikingly, the proinflammatory effect of palmitate was potently repressed by palmitoleate. This repression was not due to reduced palmitate uptake but linked to increased neutral lipid storage and enhanced cellular oxidative capacity brought about by palmitoleate's ability to restrain palmitate-induced mitochondrial dysfunction