Publications by authors named "Toby Toward"

Objectives: Stiripentol, fenfluramine, and cannabidiol are licensed add-on therapies to treat seizures in Dravet Syndrome (DS). There are no direct or indirect comparisons assessing their full licensed dose regimens, across different jurisdictions, as first-line add-on therapies in DS.

Methods: We conducted a systematic review and frequentist network meta-analysis (NMA) of randomized controlled trial (RCT) data for licensed add-on DS therapies.

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Introduction: Dravet syndrome (DS) is a rare, lifelong epileptic encephalopathy characterised by frequent and severe seizures associated with premature mortality. Typically diagnosed in infancy, patients also experience progressive behavioural, motor-function and cognitive decline. Twenty percent of patients do not reach adulthood.

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Article Synopsis
  • - Dravet syndrome (DS) is a rare condition that affects both seizure frequency and overall health-related quality of life (HRQoL), prompting a need for a more comprehensive measure of treatment effectiveness beyond just seizures.
  • - This study combined survey data on symptoms and care needs from 75 pediatric DS patients to create composite scores reflecting physical, psychosocial, and care aspects of the syndrome, finding strong links between these scores and various seizure measures.
  • - While strong associations emerged between symptom severity and seizure frequency, only behavioral issues and severe seizures significantly impacted HRQoL, indicating a need for better tools in evaluating the overall patient experience in DS.
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Background: Inhaled mannitol (Bronchitol) is licensed in Australia as a safe and efficacious addition to best supportive care in patients with cystic fibrosis.

Objective: The objective of this study was to assess the cost effectiveness of inhaled mannitol (in addition to best supportive care) in the Australian setting from the perspective of a government-funded national healthcare system.

Methods: A probabilistic patient-level simulation Markov model estimated life-time costs and outcomes of mannitol when added to best supportive care, compared with best supportive care alone in patients aged 6 years and older.

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Objective: To assess the cost-effectiveness of bivalirudin versus heparin and glycoprotein IIb/IIIa inhibitor (H-GPI) in patients undergoing primary percutaneous coronary intervention (PPCI) for acute ST-segment elevation myocardial infarction (STEMI), from a UK health service perspective.

Design: Cost-utility analysis with life-long time horizon.

Main Outcome Measures: Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness.

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This study investigated whether a correlation between leukocyte-derived elastolytic activity, alveolar epithelial type-1 cell damage, and leukocyte infiltration of the airways existed in guinea-pigs chronically exposed to inhaled lipopolysaccharide (LPS). The airway pathology of this model, notably the neutrophilia, resembles chronic obstructive pulmonary disease (COPD). The effect of the corticosteroid, dexamethasone, or the phosphodiesterase-4 (PDE4)-inhibitor, rolipram, on these features was studied.

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The relationships between changes in in vivo airway reactivity and levels cyclicAMP and cyclicGMP were determined in guinea-pig lungs after exposure to inhaled lipopolysaccharide (LPS). After LPS (30 microg.ml(-1), 1 h), guinea-pigs displayed in vivo airway hyperreactivity (AHR) at 1 h and hyporeactivity (AHOR) at 48 h, to inhaled (20 s) histamine (1 or 3 mM, respectively).

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Phosphodiesterase (PDE)-5 degrades guanosine 3',5'cyclic monophosphate (cGMP) and its inhibitor sildenafil citrate (Viagra) treats erectile dysfunction by smooth muscle relaxation through elevated cGMP. Sildenafil was examined in two guinea pig models of airways disease: guinea pigs exposed to LPS or sensitized guinea pigs with atopy exposed to ovalbumen. Ovalbumen exposure caused early- and late-phase bronchoconstrictor responses, measured in conscious animals by whole-body plethysmography.

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The effects of chronic exposures (nine, 48 h apart) of conscious guinea pigs to lipopolysaccharide (LPS) (30 microg. ml(-1), 1 h) on airway function, airway histology (in particular, goblet cell numbers), and inflammatory cell infiltration of the lungs were examined as a model of chronic inflammatory lung disease, such as chronic obstructive pulmonary disease. The sensitivity of these parameters to treatment with the corticosteroid, dexamethasone, or the phosphodiesterase-4 (PDE4) inhibitor, rolipram, was determined.

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