Computational sensing of herpes simplex virus using a cost-effective on-chip microscope.

Caused by the herpes simplex virus (HSV), herpes is a viral infection that is one of the most widespread diseases worldwide. Here we present a computational sensing technique for specific detection of HSV using both viral immuno-specificity and the physical size range of the viruses. This label-free approach involves a compact and cost-effective holographic on-chip microscope and a surface-functionalized glass substrate prepared to specifically capture the target viruses. To enhance the optical signatures of individual viruses and increase their signal-to-noise ratio, self-assembled polyethylene glycol based nanolenses are rapidly formed around each virus particle captured on the substrate using a portable interface. Holographic shadows of specifically captured viruses that are surrounded by these self-assembled nanolenses are then reconstructed, and the phase image is used for automated quantification of the size of each particle within our large field-of-view, ~30 mm2. The combination of viral immuno-specificity due to surface functionalization and the physical size measurements enabled by holographic imaging is used to sensitively detect and enumerate HSV particles using our compact and cost-effective platform. This computational sensing technique can find numerous uses in global health related applications in resource-limited environments.

Cost-effectiveness analysis of treatment of venous thromboembolism with rivaroxaban compared with combined low molecular weight heparin/vitamin K antagonist.

BACKGROUND: Venous thromboembolism (VTE) is a burden on healthcare systems. Standard treatment involves parenteral anticoagulation overlapping with a vitamin K antagonist, an approach that is effective but associated with limitations including the need for frequent coagulation monitoring. The direct oral anticoagulant rivaroxaban is similarly effective to standard therapy as a single-drug treatment for VTE and does not require routine coagulation monitoring. The objective of this economic evaluation was to estimate the cost-effectiveness of rivaroxaban compared with standard VTE treatment from a UK perspective. METHODS: A Markov model was constructed using data and probabilities derived from the EINSTEIN DVT and EINSTEIN PE studies of rivaroxaban and other published sources. Health outcomes included VTE rates, bleeding events avoided, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). RESULTS: There was greater discounted quality-adjusted life expectancy with rivaroxaban than with standard therapy, irrespective of indication and treatment duration. Rivaroxaban was associated with per-patient cost savings for each treatment duration modelled (3, 6 and 12 months), and these were greatest with shorter durations. Rivaroxaban was found to be dominant (cheaper and more effective) and, therefore, cost-effective, in both patients with deep vein thrombosis and pulmonary embolism in all three treatment duration groups, and was also cost-effective in patients requiring lifelong anticoagulation (ICERs: £8677 per QALY and £7072 per QALY in patients with index deep vein thrombosis and pulmonary embolism, respectively). The cost-effectiveness of rivaroxaban was largely insensitive to variations in one-way sensitivity analysis. Probabilistic sensitivity analysis demonstrated that at a threshold of £20,000 per QALY, rivaroxaban had a consistent probability of being cost-effective, compared with LMWH/VKA treatment, of around 80% regardless of index VTE or duration of anticoagulation therapy (3, 6, 12 months or lifelong). CONCLUSIONS: This analysis suggests that rivaroxaban represents a cost-effective choice for acute treatment of deep vein thrombosis and pulmonary embolism and secondary prevention of VTE in the UK, compared with LMWH/VKA treatment, regardless of the required treatment duration.

Cost-effectiveness of once daily GLP-1 receptor agonist lixisenatide compared to bolus insulin both in combination with basal insulin for the treatment of patients with type 2 diabetes in Norway.

BACKGROUND: Lixisenatide is a potent, selective and short-acting once daily prandial glucagon-like peptide-1 receptor agonist which lowers glycohemoglobin and body weight by clinically significant amounts in patients with type 2 diabetes treated with basal insulin, with limited risk of hypoglycemia. OBJECTIVE: To assess the cost-effectiveness of lixisenatide versus bolus insulin, both in combination with basal insulin, in patients with type 2 diabetes in Norway. METHODS: The IMS CORE Diabetes Model, a non-product-specific and validated simulation model, was used to make clinical and cost projections. Transition probabilities, risk adjustments and the progression of complication risk factors were derived from the UK Prospective Diabetes Study, supplemented with Norwegian data. Patients were assumed to receive combination treatment with basal insulin, lixisenatide or bolus insulin therapy for 3 years, followed by intensification of a basal-bolus insulin regimen for their remaining lifetime. Simulated healthcare costs, taken from the public payer perspective, were derived from microcosting and diagnosis related groups, discounted at 4% per annum and reported in Norwegian krone (NOK). Productivity costs were also captured based on extractions from the Norwegian Labor and Welfare Administration. Health state utilities were derived from a systematic literature review. Sensitivity and scenario analyses were performed. RESULTS: Lixisenatide in combination with basal insulin was associated with increased quality-adjusted life years (QALYs) and reduced lifetime healthcare costs compared to bolus insulin in combination with basal insulin in patients with Type 2 diabetes, and can be considered dominant. The net monetary benefit of lixisenatide versus bolus insulin was NOK 39,369 per patient. Results were sensitive to discounting, the application of excess body weight associated disutility and uncertainty surrounding the changes in HbA1c. CONCLUSIONS: Lixisenatide may be considered an economically efficient therapy in combination with basal insulin in the Norwegian setting, due to cost savings, weight loss and associated gains in health-related quality of life.

High-throughput and label-free single nanoparticle sizing based on time-resolved on-chip microscopy.

Sizing individual nanoparticles and dispersions of nanoparticles provides invaluable information in applications such as nanomaterial synthesis, air and water quality monitoring, virology, and medical diagnostics. Several conventional nanoparticle sizing approaches exist; however, there remains a lack of high-throughput approaches that are suitable for low-resource and field settings, i.e., methods that are cost-effective, portable, and can measure widely varying particle sizes and concentrations. Here we fill this gap using an unconventional approach that combines holographic on-chip microscopy with vapor-condensed nanolens self-assembly inside a cost-effective hand-held device. By using this approach and capturing time-resolved in situ images of the particles, we optimize the nanolens formation process, resulting in significant signal enhancement for the label-free detection and sizing of individual deeply subwavelength particles (smaller than λ/10) over a 30 mm(2) sample field-of-view, with an accuracy of ±11 nm. These time-resolved measurements are significantly more reliable than a single measurement at a given time, which was previously used only for nanoparticle detection without sizing. We experimentally demonstrate the sizing of individual nanoparticles as well as viruses, monodisperse samples, and complex polydisperse mixtures, where the sample concentrations can span ∼5 orders-of-magnitude and particle sizes can range from 40 nm to millimeter-scale. We believe that this high-throughput and label-free nanoparticle sizing platform, together with its cost-effective and hand-held interface, will make highly advanced nanoscopic measurements readily accessible to researchers in developing countries and even to citizen-scientists, and might especially be valuable for environmental and biomedical applications as well as for higher education and training programs.

Economic analysis of rivaroxaban for the treatment and long-term prevention of venous thromboembolism in Portugal.

INTRODUCTION: Venous thromboembolism is a burden on healthcare systems. The aim of this analysis was to project the long-term costs and outcomes for rivaroxaban compared to standard of care (enoxaparin/warfarin) in Portugal for the treatment and secondary prevention of venous thromboembolism. MATERIAL AND METHODS: A Markov model was developed using event rates extracted from the EINSTEIN trials supplemented with literature-based estimates of longer-term outcomes. Core outcomes included per patient costs and quality-adjusted life years reported separately per treatment arm and incrementally, as well as cost per quality-adjusted life years gained. The deep vein thrombosis and pulmonary embolism indications were analysed separately. The analyses were conducted from the Portuguese societal perspective and over a 5-year time horizon. Costs and outcomes were discounted at a 5% annual rate. Several scenario analyses were undertaken to explore the impact on results of varying key modeling assumptions. RESULTS: Rivaroxaban treatment was associated with cost-savings for the treatment of deep vein thrombosis and was both cost-saving and more effective for the treatment of pulmonary embolism, compared with enoxaparin/warfarin. DISCUSSION: The results of the sensitivity and scenario analyses further supported that rivaroxaban is a cost-effective alternative to standard of care treatment. The use of an expert panel to derive some input values and the lack of Portuguese specific utilities were the main limitations. CONCLUSION: Rivaroxaban represents an efficient alternative to using enoxaparin/warfarin in Portugal, as it's associated with lower costs (for both indications) and greater quality adjusted life years (for the pulmonary embolism indication).

Introdução: O tromboembolismo venoso representa uma carga substancial para os sistemas de saúde. O objectivo foi estimar os resultados clínicos e económicos a longo-prazo associados a rivaroxabano relativamente à prática clínica (enoxaparina/varfarina) no tratamento e prevenção secundária de tromboembolismo venoso em Portugal.Material e Métodos: Foi desenvolvido um modelo de Markov baseado nos ensaios clínicos EINSTEIN e dados da literatura para complicações a longo-prazo. Foram avaliados custos e anos de vida ajustados pela qualidade de vida totais e incrementais e rácio custo-efectividade incremental. As indicações trombose venosa profunda e embolismo pulmonar foram analisados separadamente. Adoptou-se a perspectiva da sociedade portuguesa e um horizonte temporal de cinco anos. Aplicou-se uma taxa de actualização de cinco por cento para custos e consequências. Foram desenvolvidas análises de sensibilidade e diversas análises de cenário para avaliação da variação dos resultados em função de determinados pressupostos.Resultados: Rivaroxabano está associado a menores custos na trombose venosa profunda e constitui uma alternativa associada a menores custos e a maior eficácia no tratamento de embolismo pulmonar, relativamente a enoxaparina/varfarina.Discussão: O recurso a um painel de peritos para identificação de alguns recursos e a ausência de utilidades específicas para Portugal constituem as principais limitações.Conclusão: Rivaroxabano constitui uma alternativa eficaz, estando associado a menores custos (para ambas as indicações) e a mais anos de vida ajustados pela qualidade de vida (para embolismo pulmonar) relativamente a enoxaparina/varfarina em Portugal.

Cost-effectiveness of rivaroxaban for stroke prevention in atrial fibrillation in the Portuguese setting.

INTRODUCTION AND AIMS: To project the long-term cost-effectiveness of treating non-valvular atrial fibrillation (AF) patients for stroke prevention with rivaroxaban compared to warfarin in Portugal. METHODS: A Markov model was used that included health and treatment states describing the management and consequences of AF and its treatment. The model's time horizon was set at a patient's lifetime and each cycle at three months. The analysis was conducted from a societal perspective and a 5% discount rate was applied to both costs and outcomes. Treatment effect data were obtained from the pivotal phase III ROCKET AF trial. The model was also populated with utility values obtained from the literature and with cost data derived from official Portuguese sources. The outcomes of the model included life-years, quality-adjusted life-years (QALYs), incremental costs, and associated incremental cost-effectiveness ratios (ICERs). Extensive sensitivity analyses were undertaken to further assess the findings of the model. As there is evidence indicating underuse and underprescription of warfarin in Portugal, an additional analysis was performed using a mixed comparator composed of no treatment, aspirin, and warfarin, which better reflects real-world prescribing in Portugal. RESULTS: This cost-effectiveness analysis produced an ICER of €3895/QALY for the base-case analysis (vs. warfarin) and of €6697/QALY for the real-world prescribing analysis (vs. mixed comparator). The findings were robust when tested in sensitivity analyses. CONCLUSION: The results showed that rivaroxaban may be a cost-effective alternative compared with warfarin or real-world prescribing in Portugal.

A cost-effectiveness analysis of subcutaneous interferon beta-1a 44mcg 3-times a week vs no treatment for patients with clinically isolated syndrome in Sweden.

OBJECTIVE: To assess the cost-effectiveness of subcutaneous interferon (sc IFN) beta-1a 44 mcg 3-times weekly (tiw) vs no treatment at reducing the risk of conversion to multiple sclerosis (MS) in patients with clinically isolated syndrome (CIS) in Sweden. METHODS: A Markov model was constructed to simulate the clinical course of patients with CIS treated with sc IFN beta-1a 44 mcg tiw or no treatment over a 40-year time horizon. Costs were estimated from a societal perspective in 2012 Swedish kronor (SEK). Treatment efficacy data were derived from the REFLEX trial; resource use and quality-of-life (QoL) data were obtained from the literature. Costs and outcomes were discounted at 3%. Sensitivity analyses explored whether results were robust to changes in input values and use of Poser criteria. RESULTS: Using McDonald criteria sc IFN beta-1a was cost-saving and more effective (i.e., dominant) vs no treatment. Gains in progression free life years (PFLYs) and quality-adjusted life-years (QALYs) were 1.63 and 0.53, respectively. Projected cost savings were 270,263 SEK. For Poser criteria cost savings of 823,459 SEK were estimated, with PFLY and QALY gains of 4.12 and 1.38, respectively. Subcutaneous IFN beta-1a remained dominant from a payer perspective. Results were insensitive to key input variation. Probabilistic sensitivity analysis estimated a 99.9% likelihood of cost-effectiveness at a willingness-to-pay threshold of 500,000 SEK/QALY. CONCLUSION: Subcutaneous IFN beta-1a is a cost-effective option for the treatment of patients at high risk of MS conversion. It is associated with lower costs, greater QALY gains, and more time free of MS. LIMITATIONS: The risk of conversion from CIS to MS was extrapolated from 2-year trial data. Treatment benefit was assumed to persist over the model duration, although long-term data to support this are unavailable. Cost and QoL data from MS patients were assumed applicable to CIS patients.