Trial application of a model of resource utiliztion, costs, and outcomes for stroke (MORUCOS) to assist priority setting in stroke.

Background and Purpose— Cost-effectiveness data for stroke interventions are limited, and comparisons between studies are confounded by methodological inconsistencies. The aim of this study was to trial the use of the intervention module of the economic model, a Model of Resource Utilization, Costs, and Outcomes for Stroke (MORUCOS) to facilitate evaluation and ranking of the options.

Methods— The approach involves using an economic model together with added secondary considerations. A consistent approach was taken using standard economic evaluation methods. Data from the North East Melbourne Stroke Incidence Study (NEMESIS) were used to model "current practice" (base case), against which 2 interventions were compared. A 2-stage process was used to measure benefit: health gains (expressed in disability-adjusted life years [DALYs]) and filter analysis. Incremental cost-effectiveness ratios (ICERs) were calculated, and probabilistic uncertainty analysis was undertaken.

Results— Aspirin, a low-cost intervention applicable to a large number of stroke patients (9153 first-ever cases), resulted in modest health benefits (946 DALYs saved) and a mean ICER (based on incidence costs) of US $1421 per DALY saved. Although the health gains from recombinant tissue-type plasminogen activator (rtPA) were less (155 DALYs saved), these results were impressive given the small number of persons (256) eligible for treatment. rtPA dominates current practice because it is more effective and cost-saving.

Conclusions— If used to assess interventions across the stroke care continuum, MORUCOS offers enormous capacity to support decision-making in the prioritising of stroke services.

UCP3 protein regulation in human skeletal muscle fibre types I, IIa andIIx is dependent on exercise intensity.

It has been proposed that mitochondrial uncoupling protein 3 (UCP3) behaves as an uncoupler of oxidative phosphorylation. In a cross-sectional study, UCP3 protein levels were found to be lower in all fibre types of endurance-trained cyclists as compared to healthy controls. This decrease was greatest in the type I oxidative fibres, and it was hypothesised that this may be due to the preferential recruitment of these fibres during endurance training. To test this hypothesis, we compared the effects of 6 weeks of endurance (ETr) and sprint (STr) running training on UCP3 mRNA expression and fibre-type protein content using real-time PCR and immunofluorescence techniques, respectively. UCP3 mRNA and protein levels were downregulated similarly in ETr and STr (UCP3 mRNA: by 65 and 50 %, respectively; protein: by 30 and 27 %, respectively). ETr significantly reduced UCP3 protein content in type I, IIa and IIx muscle fibres by 54, 29 and 16 %, respectively. STr significantly reduced UCP3 protein content in type I, IIa and IIx muscle fibres by 24, 31 and 26 %, respectively. The fibre-type reductions in UCP3 due to ETr, but not STr, were significantly different from each other, with the effect being greater in type I than in type IIa, and in type IIa than in type IIx fibres. As a result, compared to STr, ETr reduced UCP3 expression significantly more in fibre type I and significantly less in fibre types IIx. This suggests that the more a fibre is recruited, the more it adapts to training by a decrease in its UCP3 expression. In addition, the more a fibre type depends on fatty acid beta oxidation and oxidative phosphorylation, the more it responds to ETr by a decrease in its UCP3 content.

Economic evaluation of Australian stroke services: a prospective, multicenter study comparing dedicated stroke units with other care modalities

Background and Purpose: Level I evidence from randomized controlled trials demonstrates that the model of hospital care influences stroke outcomes; however, the economic evaluation of such is limited. An economic appraisal of 3 acute stroke care models was facilitated through the Stroke Care Outcomes: Providing Effective Services (SCOPES) study in Melbourne, Australia. The aim was to describe resource use up to 28 weeks poststroke for each model and examine the cost-effectiveness of stroke care units (SCUs). Methods: A prospective, multicenter, cohort study design was used. Costs and outcomes of stroke patients receiving 100% treatment in 1 of 3 inpatient care models (SCUs, mobile service, conventional care) were compared. Health-sector resource use up to 28 weeks was measured in 1999. Outcomes were thorough adherence to a suite of important clinical processes and the number of severe inpatient complications. Results: The sample comprised 395 participants (mean age 73 [SD 14], 77% first-ever strokes, males 53%). When compared with conventional care (n=84), costs for mobile service (n=209) were significantly higher (P=0.024), but borderline for SCU (n=102, P=0.08; $AUD12 251; $AUD15 903; $AUD15 383 respectively). This was primarily explained by the greater use of specialist medical services. The incremental cost-effectiveness of SCUs over conventional care was $AUD9867 per patient achieving thorough adherence to clinical processes and $AUD16 372 per patient with severe complications avoided, based on costs to 28 weeks. Conclusions: Although acute SCU costs are generally higher, they are more cost-effective than either mobile service or conventional care.

Lifetime cost of stroke subtypes in Australia: findings from the North East Melbourne stroke incidence study (NEMESIS)

Background and Purpose-: Little is known about any variations in resource use and costs of care between stroke subtypes, especially nonhospital costs. The purpose of this study was to describe the patterns of resource use and to estimate the first-year and lifetime costs for stroke subtypes.

Methods-: A cost-of-illness model was used to estimate the total first-year costs and lifetime costs of stroke subtypes for all strokes (subarachnoid hemorrhages excluded) that occurred in Australia during 1997. For each subtype, average cost per case during the first year and the present value of average cost per case over a lifetime were calculated. Resource use data obtained in the North East Melbourne Stroke Incidence Study (NEMESIS) were used.

Results-: The present value of total lifetime costs for all strokes was Aus $1.3 billion (US $985 million). Total lifetime costs were greatest for ischemic stroke (72%; Aus $936.8 million; US $709.7 million), followed by intracerebral hemorrhage (26%; Aus $334.5 million; US $253.4 million) and unclassified stroke (2%; Aus $30 million; US $22.7 million). The average cost per case during the first year was greatest for total anterior circulation infarction (Aus $28 266). Over a lifetime, the present value of average costs was greatest for intracerebral hemorrhage (Aus $73 542), followed by total anterior circulation infarction (Aus $53 020), partial anterior circulation infarction (Aus $50 692), posterior circulation infarction (Aus $37 270), lacunar infarction (Aus $34 470), and unclassified stroke (Aus $12 031).

Conclusions-: First-year and lifetime costs vary considerably between stroke subtypes. Variation in average length of total hospital stay is the main explanation for differences in first-year costs.

Informal care for stroke survivors. Results from the North East Melbourne stroke incidence study (NEMESIS)

Background and Purpose-: Informal caregivers play an important role in the lives of stroke patients, but the cost of providing this care has not been estimated. The purpose of this study was to determine the nature and amount of informal care provided to stroke patients and to estimate the economic cost of that care.

Methods-: The primary caregivers of stroke patients registered in the North East Melbourne Stroke Incidence Study (NEMESIS) were interviewed at 3, 6, and 12 months after stroke, and the nature and amount of informal care provided were documented. The opportunity and replacement costs of informal care for all first-ever-in-a-lifetime strokes (excluding subarachnoid hemorrhages) that occurred in 1997 in Australia were estimated.

Results-: Among 3-month stroke survivors, 74% required assistance with activities of daily living and received informal care from family or friends. Two thirds of primary caregivers were women, and most primary caregivers (>90%) provided care during family or leisure time. Total first-year caregiver time costs for all first-ever-in-a-lifetime strokes were estimated to be A$21.7 million (opportunity cost approach) or A$42.5 million (replacement cost approach), and the present values of lifetime caregiver time costs were estimated to be A$171.4 million (opportunity cost approach) or A$331.8 million (replacement cost approach).

Conclusions-: Informal care for stroke survivors represents a significant hidden cost to Australian society. Because our community is rapidly aging, this informal care burden may increase significantly in the future.

Blood pressure modifies retinal susceptibility to intraocular pressure elevation

Primary open angle glaucoma affects more than 67 million people. Elevated intraocular pressure (IOP) is a risk factor for glaucoma and may reduce nutrient availability by decreasing ocular perfusion pressure (OPP). An interaction between arterial blood pressure and IOP determines OPP; but the exact contribution that these factors have for retinal function is not fully understood. Here we sought to determine how acute modifications of arterial pressure will affect the susceptibility of neuronal function and blood flow to IOP challenge. Anaesthetized (ketamine:xylazine) Long-Evan rats with low (~60 mmHg, sodium nitroprusside infusion), moderate (~100 mmHg, saline), or high levels (~160 mmHg, angiotensin II) of mean arterial pressure (MAP, n = 5–10 per group) were subjected to IOP challenge (10–120 mmHg, 5 mmHg steps every 3 minutes). Electroretinograms were measured at each IOP step to assess bipolar cell (b-wave) and inner retinal function (scotopic threshold response or STR). Ocular blood flow was measured using laser-Doppler flowmetry in groups with similar MAP level and the same IOP challenge protocol. Both b-wave and STR amplitudes decreased with IOP elevation. Retinal function was less susceptible to IOP challenge when MAP was high, whereas the converse was true for low MAP. Consistent with the effects on retinal function, higher IOP was needed to attenuated ocular blood flow in animals with higher MAP. The susceptibility of retinal function to IOP challenge can be ameliorated by acute high BP, and exacerbated by low BP. This is partially mediated by modifications in ocular blood flow.

Electroretinography in streptozotocin diabetic rats following acute intraocular pressure elevation

Background
We consider whether pre-existing streptozotocin induced hyperglycemia in rats affects the ability of the eye to cope with a single episode of acute intraocular pressure (IOP) elevation.
Methods
Electroretinogram (ERG) responses were measured (−6.08 to 1.92 log cd.s.m−2) in anaesthetized (60:5 mg/kg ketamine:xylazine) dark-adapted (>12 h) adult Sprague–Dawley rats 1 week after a single acute IOP elevation to 70 mmHg for 60 min. This was undertaken in rats treated 11 weeks earlier with streptozotocin (STZ, n = 12, 50 mg/kg at 6 weeks of age) or citrate buffer (n = 12). ERG responses were analyzed to derive an index of photoreceptor (a-wave), ON-bipolar (b-wave), amacrine (oscillatory potentials) and inner retinal (positive scotopic threshold response, pSTR) function.
Results
One week following acute IOP elevation there was a significant reduction of the ganglion cell pSTR (−35 ± 11 %, P = 0.0161) in STZ-injected animals. In contrast the pSTR in citrate-injected animals was not significant changed (+16 ± 14 %). The negative component of the STR was unaffected by IOP elevation in either citrate or STZ-treated groups. Photoreceptoral (a-wave, citrate-control +4 ± 3 %, STZ +4 ± 5 %) and ON-bipolar cell (b-wave, control +4 ± 3 %, STZ +4 ± 5 %) mediated responses were not significantly affected by IOP elevation in either citrate- or STZ-injected rats. Finally, oscillatory potentials (citrate-control +8 ± 23 %, STZ +1 ± 17 %) were not reduced 1 week after IOP challenge.
Conclusions
The ganglion cell dominated pSTR was reduced following a single episode of IOP elevation in STZ diabetic, but not control rats. These data indicate that hyperglycemia renders the inner retina more susceptible to IOP elevation.

Chronic intraocular pressure elevation impairs autoregulatory capacity in streptozotocin-induced diabetic rat retina

Purpose: To assess ocular blood flow responses to acute IOP stress following 4 weeks of chronic IOP elevation in streptozotocin (STZ)-induced diabetic and control rats. We hypothesise that chronic IOP elevation for 4 weeks will further impair blood flow regulation in STZ-induced diabetic rats eyes. Methods: Two weeks following citrate buffer or STZ-injections chronic IOP elevation was induced in Long Evans rats via fortnightly intracameral injections of microspheres (15 μm) suspended in 5% polyethylene glycol. IOP was monitored daily. Electroretinography (ERG, -6.79-2.07 log cd s m-2) was undertaken at Week 4 to compare photoreceptor (RmPIII), ON-bipolar cell (Vmax) and ganglion cell dominant ERG [scotopic threshold response (STR)] components. 4 weeks post-chronic IOP induction, ocular blood flow (laser Doppler flowmetry) was measured in response to acute IOP challenge (10-100 mmHg, in 5 mmHg steps, each 3 min). Results: Four weeks of chronic IOP (mean ± S.E.M., citrate: 24.0 ± 0.3 to 30.7 ± 1.3 and STZ-diabetes: 24.2 ± 0.2 to 31.1 ± 1.2 mmHg) was associated with reduced photoreceptor amplitude in both groups (-25.3 ± 2.2% and -17.2 ± 3.0%, respectively). STZ-diabetic eyes showed reduced photoreceptor sensitivity (citrate: 0.5 ± 1.8%, STZ-diabetic: -8.1 ± 2.4%). Paradoxically ON-bipolar cell sensitivity was increased, particularly in citrate control eyes (citrate: 166.8 ± 25.9%, STZ-diabetic: 64.8 ± 18.7%). The ganglion cell dominant STR was not significantly reduced in STZ-diabetic rats. Using acute IOP elevation to probe autoregulation, we show that STZ-diabetes impaired autoregulation compared with citrate control animals. The combination of STZ-diabetes and chronic IOP elevation further impaired autoregulation. Conclusions: STZ-diabetes and chronic IOP elevation appear to be additive risk factors for impairment of ocular blood flow autoregulation.

Screening Sarah Bernhardt: reinterpreting acting in silent film

Sarah Bernhardt, the great nineteenth-century theatrical actress, was also the first major international film star. Appearing cross-dressed in a short Hamlet film before international audiences at the Paris Exposition of 1900, this 56-year-old French actress most famously went on to make Camille (La Dame aux Camélias, 1911) and Queen Elizabeth (Les Amours de la Reine Elisabeth, 1912). Later appearing in one of the first celebrity home movies (Sarah Bernhardt at Home, 1915), she also made a WWI propaganda film, Mothers of France (Mères Françaises, 1917). This presentation explores these films as evidence of a productive exchange between the stage and the nascent film industry. Rather than see Bernhardt’s acting as evidence of the theatre’s incommensurability with film, it will demonstrate the legacy of her stage acting as she adapted it to early film. The talk will include screenings of the films accompanied by live music.

Biocompatible and biodegradable Mg/Mg composite foam for bone tissue engineering.

This thesis focuses on studying solid and porous Magnesium-composite structures. Magnesium is attracting increasing interest as promising biodegradable material for medical applications; however, suffering from low mechanical properties. This thesis suggests the manufacturing and application of a new approach that is high str