Healthcare resource use associated with the diagnosis of transthyretin amyloidosis cardiomyopathy

Objectives Our primary aim was to evaluate the healthcare resource use associated with the diagnosis of transthyretin amyloidosis cardiomyopathy. Second, we aim to assess the effect of the number of diagnostic tests and clinical contact points on the total time and costs between symptom onset and diagnosis defining a quantitative hypothetical optimized diagnostic pathway. Setting Clinical and cost data were collected from patients presenting between 2010 and 2018 in a tertiary referral institution in South London involving two participating hospitals. Participants Thirty-eight adult patients with a definite diagnosis of transthyretin amyloidosis cardiomyopathy were included, mostly male (n = 28, 74%) and of African-Caribbean descent (n = 23, 64%). We excluded patients without a confirmed transthyretin amyloidosis cardiomyopathy or those on inotersen, patisiran, or diflunisal at point of referral. Primary and secondary outcome measures The average time between first presentation and final diagnosis, and the cost per patient per month. By comparing to a more optimal clinical pathway towards diagnosis, we considered what could be the theoretical gain in terms of time to diagnosis and financial savings. Results The average time between first presentation and final diagnosis was 2.74 years. The average cost per patient per month was higher with progressive heart failure symptoms. A hypothetical optimal pathway reduces time to diagnosis of 1.65 to 1.74 years per patient. The potential financial savings are estimated within the range of £3000 to £4800 per patient. Conclusions Patients diagnosed with transthyretin amyloidosis cardiomyopathy have substantial healthcare resource utilization and costs starting from symptom onset. Higher costs were observed with progression in symptoms and appear linked to a delayed diagnosis. The number of additional diagnostic tests and clinical contact points may contribute to this and could represent a path to explore further for important health and cost savings, with more efficient pathways for these patients to be managed

Economic impact of introducing TYRX amongst patients with heart failure and reduced ejection fraction undergoing implanted cardiac device procedures: a retrospective model based cost analysis

BACKGROUND AND AIMS: Infection is a serious and expensive complication of Cardiac Implantable Electronic Device (CIED) procedures. A retrospective based cost analysis was performed to estimate Trust level savings of using the TYRX antibacterial envelope as a primary prevention measure against infection in a tertiary referral centre in South London, UK. METHODS: A retrospective cohort of heart failure patients with reduced ejection fraction undergoing Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronization Therapy (CRT) procedures were evaluated. Decision-analytic modelling was performed to determine economic savings of using the envelope during CIED procedure vs CIED procedure alone. RESULTS: Over a 12 month follow-up period following CIED procedure, the observed infection rate was 3.14% (n = 5/159). The average cost of a CIED infection inpatient admission was £41,820 and, further to economic analysis, the additional costs attributable to infection was calculated at £62,213.94. A cost saving of £624 per patient by using TYRX during CIED procedure as a primary preventative measure against infection was estimated. CONCLUSIONS: TYRX would be a cost-saving treatment option amongst heart failure patients undergoing ICD and CRT device procedures based on analysis in the local geographical area of South London. If upscaled to the UK population, we estimate potential cost savings for the National Health Service (NHS)

Health Economics, Economic Evaluation and Artificial Intelligence Technology

Health economics is the study of allocating scarce goods within a healthcare market. Due to constrained budgets, clinical effectiveness is not enough to inform healthcare planning and provision. Economic evaluation enables the assessment of value for money through the comparative analysis of the costs and consequences of alternative courses of action. It considers the forfeited benefits and opportunity cost of not committing resources to an alternative choice. In this chapter, we introduce health economics and analytical methods within economic evaluation. Challenges arising when evaluating medical technology and artificial intelligences are presented along with a tool intended to improve the assessment of their value

Global adaptation to a lipid environment triggers the dormancy-related phenotype of Mycobacterium tuberculosis

Strong evidence supports the idea that fatty acids rather than carbohydrates are the main energy source of Mycobacterium tuberculosis during infection and latency. Despite that important role, a complete scenario of the bacterium's metabolism when lipids are the main energy source is still lacking. Here we report the development of an in vitro model to analyze adaptation of M. tuberculosis during assimilation of long-chain fatty acids as sole carbon sources. The global lipid transcriptome revealed a shift toward the glyoxylate cycle, the overexpression of main regulators whiB3, dosR, and Rv0081, and the increased expression of several genes related to reductive stress. Our evidence showed that lipid storage seems to be the selected mechanism used by M. tuberculosis to ameliorate the assumed damage of reductive stress and that concomitantly the bacilli acquired a slowed-growth and drug-tolerant phenotype, all characteristics previously associated with the dormant stage. Additionally, intergenic regions were also detected, including the unexpected upregulation of tRNAs that suggest a new role for these molecules in the acquisition of a drug-tolerant phenotype by dormant bacilli. Finally, a set of lipid signature genes for the adaptation process was also identified. This in vitro model represents a suitable condition to illustrate the participation of reductive stress in drugs' activity against dormant bacilli, an aspect scarcely investigated to date. This approach provides a new perspective to the understanding of latent infection and suggests the participation of previously undetected molecules. IMPORTANCE Mycobacterium tuberculosis establishes long-lasting highly prevalent infection inside the human body, called latent tuberculosis. The known involvement of fatty acids is changing our understanding of that silent infection; however, question of how tubercle bacilli globally adapt to a lipid-enriched environment is still an unanswered. With the single change of providing fatty acids as carbon sources, the bacilli switch on their program related to dormant stage: slowed growth, accumulation of lipid bodies, and development of drug tolerance. In this stage, unexpected and previously unknown participants were found to play putatively important roles during the process. For the first time, this work compares the global transcriptomics of bacteria by using strand-specific RNA sequencing under two different growth conditions. This study suggests novel targets for the control of tuberculosis and provides a new straightforward in vitro model that could help to test the activity of drugs against dormant bacilli from a novel perspective