Evaluation of health economic impact of initial diagnostic modality selection for colorectal cancer liver metastases in suspected patients in China, Japan and the USA.

AIMS: To compare cost offsets and contributing factors (false-negative rates and confirmatory imaging requirements, potentially leading to longer waiting times for diagnosis) as well as long-term cost effectiveness associated with the diagnostic and treatment pathways for colorectal cancer liver metastases (CRCLM) in the US, Japan, and China according to initial imaging modality used. Gadoxetate disodium (ethoxylbenzyl-diethylenetriaminepentaacetic acid)-enhanced magnetic resonance imaging (EOB-MRI) was compared to multidetector computed tomography (MDCT), extracellular contrast media enhanced-MRI (ECCM-MRI) (the US and China only) and contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: Decision tree models were developed to simulate the clinical pathway, from first diagnostic test to initial treatment decision, based on local clinical guidelines and validated by experts. Input data were derived from the literature (up to 31st December 2020) as well as from interviews with local experts. A Markov model extension was built to evaluate the number of false-negative patients and associated costs, over a lifetime horizon. RESULTS: The decision-tree models showed that, increasing proportionate use of initial EOB-MRI resulted in a cost-offset per patient (excluding false-negative patients) in all countries (USD 201 for the US, JPY 6,284 for Japan and CNY 446 for China) driven by reductions in follow-on diagnostic procedures and unnecessary treatment. The use of EOB-MRI was also associated with a shorter average waiting time to a final diagnosis and treatment decision compared to MDCT, ECCM-MRI and CEUS. The Markov model showed that with an increase in EOB-MRI use, there are fewer false-negative diagnoses over a lifetime horizon. In all three countries, the incremental cost-effectivenes ratio (ICER) was below standard willingness-to-pay thresholds. CONCLUSION: The findings of these models demonstrate that use of EOB-MRI early in the diagnostic pathway for CRCLM results in short-term cost savings, as well as being cost effective in the long term.

Impact of non-adherence to direct oral anticoagulants amongst Swedish patients with non-valvular atrial fibrillation: results from a real-world cost-utility analysis.

AIMS: A third of non-valvular atrial fibrillation (NVAF) patients are non-adherent to direct oral anticoagulants (DOACs). Estimates of the economic value of full adherence and the cost of two types of adherence improving interventions are important to healthcare planners and decision-makers. METHODS: A cost-utility analysis estimated the impact of non-adherence over a 20-year horizon, for a patient cohort with a mean age of 77 years, based on data from the Stockholm Healthcare database of NVAF patients with incident stroke between 2011 and 2018. Adherence was defined using a medication possession ratio (MPR) cut-off of 90%; primary outcomes were the number of ischemic strokes and associated incremental cost-utility ratio. RESULTS: Hypothetical comparisons between cohorts of 1,000 patients with varying non-adherence levels and full adherence (MPR >90%) predicted an additional number of strokes ranging from 117 (MPR = 81-90%) to 866 (MPR <60%), and years of life lost ranging from 177 (MPR = 81- 90%) to 1,318 (MPR < 60%; discounted at 3%). Chronic disease co-management intervention occurring during each DOAC prescription renewal and patient education intervention at DOAC initiation will be cost-saving to the health system if its cost is below SEK 143 and SEK 4,655, and cost-effective if below SEK 858 and SEK 28,665, respectively. CONCLUSION: Adherence improving interventions for NVAF patients on DOACs such as chronic disease co-management and patient education can be cost-saving and cost-effective, within a range of costs that appear reasonable to the Swedish healthcare system.

Atrial fibrillation (AF) is the most common type of chronic cardiac arrhythmia and a major risk factor for ischemic stroke (IS). The objective of this study was to compare the costs and health outcomes associated with adherence to direct oral anticoagulant (DOAC) therapy in Sweden. The study also aimed to demonstrate the potential benefits of developing interventions to improve DOAC adherence. DOAC therapy (DOACs; apixaban, dabigatran, edoxaban, and rivaroxaban) has been approved in Europe for the prevention of stroke in adult patients with AF. It has been demonstrated to provide warfarin-similar reductions in stroke risk in NVAF patients, with reductions in mortality and intracranial hemorrhage. However, non-adherence to DOAC medication prevents patients and healthcare systems from fully benefiting from DOAC therapy, resulting in a lower benefit than those seen in randomized controlled trials. DOAC non-adherence is where AF patients deviate from the DOAC treatment regimen as prescribed by health providers. This study suggested that non-adherence to DOAC therapy has a substantial impact on ischemic stroke risk and significant additional healthcare system costs. Patient education and chronic disease co-management (two types of DOAC adherence improving intervention) can be cost-saving and cost-effective within a range of costs that appear reasonable to the Swedish healthcare system. Healthcare policy-makers should prioritize initiatives aimed at improving DOAC adherence in order to improve outcomes in AF.

Evaluation of the health economic impact of initial diagnostic modality selection in patients suspected of having HCC in China and the USA.

AIMS: To compare relative costs associated with the diagnostic pathways for hepatocellular carcinoma (HCC) in the US and China according to the initial imaging modality used. Gadoxetate disodium (ethoxylbenzyl-diethylenetriaminepentaacetic acid)-enhanced magnetic resonance imaging (EOB-MRI) was compared to contrast-enhanced multidetector computed tomography (MDCT), extracellular contrast media enhanced-MRI (ECCM-MRI) and contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: Decision tree models were developed to simulate the clinical pathway, based on local clinical guidelines, and validated by experts. Input data were derived from the literature (up to 31 December 2020) as well as from interviews with local experts. RESULTS: The models showed that compared to alternative initial imaging modalities, EOB-MRI was associated with higher diagnostic accuracy (fewer false-positive and fewer false-negative results). Increasing proportionate use of EOB-MRI resulted in a cost offset per patient (excluding false-negative patients) in both the US (USD 337) and China (CNY 1,443), driven by reductions in scan costs and unnecessary treatment costs. The use of EOB-MRI was also associated with a shorter average waiting time for a final diagnosis and treatment decision for patients compared to MDCT, ECCM-MRI, and CEUS. CONCLUSION: The findings of these models demonstrate that EOB-MRI is the most accurate and rapid imaging modality for the diagnosis of HCC in the US and China, resulting in cost offsets that may benefit the healthcare system.

Palladium- and nickel-catalyzed Kumada cross-coupling reactions of gem-difluoroalkenes and monofluoroalkenes with Grignard reagents.

A novel Kumada-Tamao-Corriu cross-coupling reaction of gem-di- or monofluoroalkenes with Grignard reagents, with or without ß-hydrogen atoms, in the presence of a catalytic amount of palladium- or nickel-based catalysts has been developed. The reaction is performed under mild conditions (room temperature or reflux in diethyl ether for 1-2 h) and leads to di-cross- or mono-cross-coupled products in good to high yields.

Transition-metal-free Sonogashira-type cross-coupling of alkynes with fluoroarenes.

A novel, inexpensive, and efficient palladium-, copper-, ligand-, and amine-free Sonogashira-type cross-coupling reaction of terminal alkynes with unreactive aryl fluorides in the presence of sodium, sodium methoxide, and calcium hydroxide under the assistance of a Grignard reagent was developed. A plausible mechanism was also suggested.