Device-specific infection rates for high-risk patients were not available in the literature and not used in this analysis, potentially under-estimating the impact of TYRX in certain devices. Nevertheless, TYRX is associated with a reduction in post-operative infection risk relative to SOC, resulting in reduced healthcare resource utilization at an initial cost. The ICERs are below the accepted willingness-to-pay thresholds used by UK decision-makers. TYRX, therefore, represents a cost-effective prevention option for CIED patients at high-risk of post-operative infection.

Six normal males and eight male subjects with alcoholic liver disease (ALD) and ascites were given a single 500-mg dose of erythromycin base. Twelve serum samples were collected at 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, and 24 h after dosing and assayed microbiologically for erythromycin concentration. Absorption was characterized by a zero-order model for both groups. ALD subjects demonstrated a shorter lag time (2.0 versus 3.0 h), an earlier peak (4.6 versus 6.3 h, P less than 0.05), and higher peak concentrations (2.04 versus 1.50 micrograms/ml) than normal subjects. Previously unreported biphasic elimination kinetics after oral dosing were observed in five and four ALD subjects. In the ALD group, the mean half lives for the first (alpha) and terminal (beta) phases were 1.6 and 4.5 h, respectively, and in normal subjects, were 1.3 and 6.6 h. The difference in alpha between groups was significant, P less than 0.05. The clinical significance of this finding for ALD patients receiving prolonged courses of erythromycin is discussed.

Aims To develop a novel interactive budget impact model that assesses affordability of diabetes treatments in specific populations, and to test the model in a hypothetical scenario by estimating cost savings resulting from reduction in HbA1c from ≥69 mmol/mol (8.5%) to a target of 53 mmol/mol (7.0%) in adults with Type 1 diabetes in the UK. Methods A dynamic, interactive model was created using the projected incidence and progression over a 5‐year horizon of diabetes‐related complications (micro‐ and macrovascular disease, severe hypoglycaemia and diabetic ketoacidosis) for different HbA1c levels, with flexible input of population size, complications and therapy costs, HbA1c distribution and other variables. The model took a National Health Service and societal perspective. Results The model was developed, and in the proposed hypothetical situation, reductions in complications and expected costs evaluated. Achievement of target HbA1c in individuals with HbA1c ≥69 mmol/mol (8.5%) would reduce expected chronic complications from 6.8 to 1.2 events per 100 person‐years, and diabetic ketoacidosis from 14.5 to 1.0 events per 100 person‐years. Potential cumulative direct cost savings achievable in the modelled population were estimated at £687 m over 5 years (£5,585/person), with total (direct and indirect) savings of £1,034 m (£8,400/person). Conclusions Implementation of strategies aimed at achieving target glucose levels in people with Type 1 diabetes in the UK has the potential to drive a significant reduction in complication costs. This estimate may provide insights into the potential for investment in achieving savings through improved diabetes care in the UK.

Objective Prevention of recurrent stroke in patients with embolic stroke of undetermined source (ESUS) is challenging. The advent of safer anticoagulation in the form of direct oral anticoagulants (DOACs) has prompted exploration of prophylactic anticoagulation for all ESUS patients, rather than anticoagulating just those with documented atrial fibrillation (AF). However, recent trials have failed to demonstrate a clinical benefit, while observing increased bleeding. We modeled the economic impact of anticoagulating ESUS patients without documented AF across multiple geographies. Methods CRYSTAL-AF trial data were used to assess ischaemic stroke event rates in ESUS patients confirmed AF-free after long-term monitoring. Anticipated bleeding event rates (including both minor and major bleeds) with aspirin, dabigatran 150 mg, and rivaroxaban 20 mg were sourced from published meta-analyses, whilst a 30% ischaemic stroke reduction for both DOACs was assumed. Cost data for clinical events and pharmaceuticals were collected from the local payer perspective. Results Compared with aspirin, dabigatran and rivaroxaban resulted in 17.9 and 29.9 additional bleeding events per 100 patients over a patient’s lifetime, respectively. Despite incorporating into our model the proposed 30% reduction in ischaemic stroke risk, both DOACs were cost-additive over patient lifetime, as the costs of bleeding events and pharmaceuticals outweighed cost savings associated with the reduction in ischaemic strokes. DOACs added £5953–£7018 per patient (UK), €6683–€7368 (Netherlands), €4933–€9378 (Spain), AUD$5353–6539 (Australia) and $26,768–$32,259 (US) of payer cost depending on the agent prescribed. Additionally, in the U.S. patient pharmacy co-payments ranged from $2468–$12,844 depending on agent and patient plan. In all settings, cost-savings could not be demonstrated even when the modelling assumed 100% protection from recurrent ischaemic strokes, due to the very low underlying risk of recurrent ischaemic stroke in this population (1.27 per 100 patient-years). Conclusions Anticoagulation of non-AF patients may cause excess bleeds and add substantial costs for uncertain benefits, suggesting a personalised approach to anticoagulation in ESUS patients.