The Health Economic Value of Changes in Glycaemic Control, Weight and Rates of Hypoglycaemia in Type 1 Diabetes Mellitus.

AIMS: Therapy-related consequences of treatment for type 1 diabetes mellitus (T1DM), such as weight gain and hypoglycaemia, act as a barrier to attaining optimal glycaemic control, indirectly influencing the incidence of vascular complications and associated morbidity and mortality. This study quantifies the individual and combined contribution of changes in hypoglycaemia frequency, weight and HbA1c to predicted quality-adjusted life-years (QALYs) within a T1DM population. MATERIALS AND METHODS: We describe the Cardiff Type 1 Diabetes (CT1DM) Model, originally informed by the Diabetes Control and Complications Trial (DCCT) and updated with the Epidemiology of Diabetes Interventions and Complications (EDIC) study and Swedish National Diabetes Registry for microvascular and cardiovascular complications respectively. We report model validation results and the QALY impact of HbA1c, weight and hypoglycaemia changes. RESULTS: Validation results demonstrated coefficients of determination for clinical endpoints of R2 = 0.863 (internal R2 = 0.999; external R2 = 0.823), costs R2 = 0.980 and QALYs R2 = 0.951. Achieving and maintaining a 1% HbA1c reduction was estimated to provide 0.61 additional discounted QALYs. Weight changes of ±1kg, ±2kg or ±3kg led to discounted QALY changes of ±0.03, ±0.07 and ±0.10 respectively, while modifying hypoglycaemia frequency by -10%, -20% or -30% resulted in changes of -0.05, -0.11 and -0.17. The differences in discounted costs, life-years and QALYs associated with HbA1c 6% versus 10% were -£19,037, 2.49 and 2.35 respectively. CONCLUSIONS: Using a model updated with contemporary epidemiological data, this study presents an outcome-focused perspective to assessing the health economic consequences of differing levels of glycaemic control in T1DM with and without weight and hypoglycaemia effects.

Vortex and half-vortex dynamics in a nonlinear spinor quantum fluid.

Vortices are archetypal objects that recur in the universe across the scale of complexity, from subatomic particles to galaxies and black holes. Their appearance is connected with spontaneous symmetry breaking and phase transitions. In Bose-Einstein condensates and superfluids, vortices are both point-like and quantized quasiparticles. We use a two-dimensional (2D) fluid of polaritons, bosonic particles constituted by hybrid photonic and electronic oscillations, to study quantum vortex dynamics. Polaritons benefit from easiness of wave function phase detection, a spinor nature sustaining half-integer vorticity, strong nonlinearity, and tuning of the background disorder. We can directly generate by resonant pulsed excitations a polariton condensate carrying either a full or half-integer vortex as initial condition and follow their coherent evolution using ultrafast imaging on the picosecond scale. The observations highlight a rich phenomenology, such as the spiraling of the half-vortex and the joint path of the twin charges of a full vortex, until the moment of their splitting. Furthermore, we observe the ordered branching into newly generated secondary couples, associated with the breaking of radial and azimuthal symmetries. This allows us to devise the interplay of nonlinearity and sample disorder in shaping the fluid and driving the vortex dynamics. In addition, our observations suggest that phase singularities may be seen as fundamental particles whose quantized events span from pair creation and recombination to 2D+t topological vortex strings.

In-hospital outcomes with thrombolytic therapy in patients with renal dysfunction presenting with acute ischaemic stroke.

BACKGROUND: Thrombolytic therapy is an effective treatment modality for acute ischaemic stroke within 3 hours of symptom onset. Its safety and efficacy have not been studied in patients with chronic kidney disease (CKD), who are known to have abnormalities in coagulation and platelet function. METHODS: We studied all patients who consecutively received intravenous thrombolytic therapy for acute stroke at our hospital from 2005-2009 (n = 74). Alteplase was administered to patients deemed eligible by National Institute of Health criteria per protocol. We studied associations between admission renal dysfunction [estimated glomerular filtration rate (eGFR) <60ml/min/1.73 m(2)] and in-hospital outcomes: intracranial haemorrhage (ICH), poor functional status (modified Rankin score 3-6) and death. RESULTS: Mean +/- SD age was 66.4 +/- 16.9 years with 39 (52.7%) men and 46 (62.2%) Caucasian. Twenty patients (27.0%) had eGFR <60 and were older, with a higher prevalence of diabetes and coronary artery disease than patients with eGFR > or =60. Presenting stroke severity, blood pressure and time to alteplase were similar in the two groups. Symptomatic ICH occurred in two patients with eGFR > or =60. Asymptomatic and symptomatic ICH considered together showed no difference in these event rates (20% in eGFR <60 vs 11.1% in eGFR > or =60, P = 0.321). There was no difference in poor functional status (70.0% in eGFR <60 vs 57.4% in eGFR > or =60, P = 0.324) or in-hospital death outcomes (10.0% in eGFR <60 vs 7.4% in eGFR > or =60, P = 0.717). Multivariate logistic regression analysis revealed no association between eGFR <60 and in-hospital outcomes, while increasing age was associated with poor functional status [odds ratio 1.03 (1.00-1.06, P = 0.047)]. CONCLUSIONS: In our limited sample size study, presence of eGFR <60 in patients receiving thrombolytic therapy for acute stroke was not found to be associated with increased ICH, poor functional outcome or death. These findings suggest that use of thrombolytics in acute stroke is appropriate in patients with renal dysfunction.

A role for cytoskeletal elements in the light-driven translocation of proteins in rod photoreceptors.

PURPOSE: Light-driven protein translocation is responsible for the dramatic redistribution of some proteins in vertebrate rod photoreceptors. In this study, the involvement of microtubules and microfilaments in the light-driven translocation of arrestin and transducin was investigated. METHODS: Pharmacologic reagents were applied to native and transgenic Xenopus tadpoles, to disrupt the microtubules (thiabendazole) and microfilaments (cytochalasin D and latrunculin B) of the rod photoreceptors. Quantitative confocal imaging was used to assess the impact of these treatments on arrestin and transducin translocation. A series of transgenic tadpoles expressing arrestin truncations were also created to identify portions of arrestin that enable arrestin to translocate. RESULTS: Application of cytochalasin D or latrunculin B to disrupt the microfilament organization selectively slowed only transducin movement from the inner to the outer segments. Perturbation of the microtubule cytoskeleton with thiabendazole slowed the translocation of both arrestin and transducin, but only in moving from the outer to the inner segments. Transgenic Xenopus expressing fusions of green fluorescent protein (GFP) with portions of arrestin implicates the C terminus of arrestin as an important portion of the molecule for promoting translocation. This C-terminal region can be used independently to promote translocation of GFP in response to light. CONCLUSIONS: The results show that disruption of the cytoskeletal network in rod photoreceptors has specific effects on the translocation of arrestin and transducin. These effects suggest that the light-driven translocation of visual proteins at least partially relies on an active motor-driven mechanism for complete movement of arrestin and transducin.