Estimating the Clinical and Economic Impact of Introducing a New Antibacterial into Greek Clinical Practice for the Management of Hospital-Acquired Infections with Limited Treatment Options.

INTRODUCTION: Hospital-acquired infections (HAIs) and growing antimicrobial resistance (AMR) represent a significant healthcare burden globally. Especially in Greece, HAIs with limited treatment options (LTO) pose a serious threat due to increased morbidity and mortality. This study aimed to estimate the clinical and economic value of introducing a new antibacterial for HAIs with LTO in Greece. METHODS: A previously published and validated dynamic model of AMR was adapted to the Greek setting. The model estimated the clinical and economic outcomes of introducing a new antibacterial for the treatment of HAIs with LTO in Greece. The current treatment pathway was compared with introducing a new antibacterial to the treatment sequence. Outcomes were assessed from a third-party payer perspective, over a 10-year transmission period, with quality-adjusted life years (QALYs) and life years (LYs) gained considered over a lifetime horizon. RESULTS: Over the next 10 years, HAIs with LTO in Greece account for approximately 1.4 million hospital bed days, hospitalisation costs of more than €320 million and a loss of approximately 403,000 LYs (319,000 QALYs). Introduction of the new antibacterial as first-line treatment provided the largest clinical and economic benefit, with savings of up to 93,000 bed days, approximately €21 million in hospitalisation costs and an additional 286,000 LYs (226,000 QALYs) in comparison to the current treatment strategy. The introduction of a new antibacterial was linked to a monetary benefit of €6.8 billion at a willingness to pay threshold of €30,000 over 10 years. CONCLUSION: This study highlights the considerable clinical and economic benefit of introducing a new antibacterial for HAIs with LTO in Greece. This analysis shows the additional benefit when a new antibacterial is introduced to treatment sequences. These findings can be used to inform decision makers to implement policies to ensure timely access to new antibacterial treatments in Greece.

Antimicrobial resistance is a major issue for the Greek healthcare system. The overuse of antibacterial agents contributes to the growing resistance levels, making currently available treatment options less effective. As a result, there is an imperative need to address antimicrobial resistance in Greece. This study developed a mathematical model to investigate the clinical and economic benefits of introducing a new antibacterial to current treatment practice. The model uses regression equations to describe the relationships between inputs and outputs from a published and validated model, which describes the transmission and treatment of infections. The model is used to estimate the impact of a new treatment in Greece, considering differing treatment sequence scenarios. The largest health and financial benefits were seen when a new antibacterial was introduced at first line prior to currently used treatments. Over 10 years, savings of up to 93,000 hospital bed days and €21 million in hospitalisation costs could be achieved, as well as a gain of 286,000 patient life years and 226,000 patient quality-adjusted life years (QALYs), a measure of a patient's quality and length of life, over their remaining lifetime. The introduction of a new antibacterial into the current treatment pathway resulted in an overall monetary benefit of €6.8 billion over 10 years, when additional QALYs are valued at €30,000. This study demonstrates considerable health economic benefits of introducing a new antibacterial in Greece and can help inform decision makers when developing a national action plan to combat resistance and improve access to treatments.

Clinical and Economic Value of Reducing Antimicrobial Resistance in the Management of Hospital-Acquired Infections with Limited Treatment Options in Greece.

INTRODUCTION: Antimicrobial resistance (AMR) is a major public health threat worldwide. Greece has the highest burden of infections due to antibiotic-resistant bacteria among European Union/European Economic Area (EU/EEA) countries. One of the most serious AMR threats in Greece is hospital-acquired infections (HAIs) with limited treatment options (LTO) caused by resistant gram-negative pathogens. Thus, this study sought to estimate the current AMR burden in Greece and the value of reducing AMR to gram-negative pathogens for the Greek healthcare system. METHODS: The current model was adapted from a previously published and validated model of AMR to investigate the overall and AMR-specific burden of treating the most common HAIs with LTO in Greece and scenarios to demonstrate the benefits associated with reducing AMR levels from a third-party payer perspective. Clinical and economic outcomes were estimated over a 10-year time horizon; life years (LYs) and quality-adjusted life years (QALYs) were calculated over a lifetime (based on the annual number of infections over 10 years) at a willingness-to-pay of €30,000 per QALY gained and a 3.5% discount rate. RESULTS: In Greece, the current AMR levels in HAIs with LTO caused by four gram-negative pathogens account for > 316,000 hospital bed days, €73 million in hospitalisation costs, and > 580,000 LYs and 450,000 QALYs lost over 10 years. The monetary burden is estimated at €13.9 billion. A reduction in current AMR levels by 10-50% results in clinical and economic benefit; 29,264-151,699 bed days may be saved, leading to decreased hospitalisation costs (€6.8 million-€35.3 million) and a gain in LYs (85,328-366,162) and QALYs (67,421-289,331), associated with a monetary benefit of between €2.0 billion and €8.7 billion. CONCLUSION: This study shows the substantial clinical and economic burden AMR represents to the Greek healthcare system and the value that can be achieved by effectively reducing AMR levels.

Diverse functions of mRNA metabolism factors in stress defense and aging of Caenorhabditis elegans.

Processing bodies (PBs) and stress granules (SGs) are related, cytoplasmic RNA-protein complexes that contribute to post-transcriptional gene regulation in all eukaryotic cells. Both structures contain translationally repressed mRNAs and several proteins involved in silencing, stabilization or degradation of mRNAs, especially under environmental stress. Here, we monitored the dynamic formation of PBs and SGs, in somatic cells of adult worms, using fluorescently tagged protein markers of each complex. Both complexes were accumulated in response to various stress conditions, but distinct modes of SG formation were induced, depending on the insult. We also observed an age-dependent accumulation of PBs but not of SGs. We further showed that direct alterations in PB-related genes can influence aging and normal stress responses, beyond their developmental role. In addition, disruption of SG-related genes had diverse effects on development, fertility, lifespan and stress resistance of worms. Our work therefore underlines the important roles of mRNA metabolism factors in several vital cellular processes and provides insight into their diverse functions in a multicellular organism.

The general control nonderepressible-2 kinase mediates stress response and longevity induced by target of rapamycin inactivation in Caenorhabditis elegans.

The general control nonderepressible 2 (GCN2) kinase is a nutrient-sensing pathway that responds to amino acids deficiency and induces a genetic program to effectively maintain cellular homeostasis. Here we established the conserved role of Caenorhabditis elegans GCN-2 under amino acid limitation as a translation initiation factor 2 (eIF2) kinase. Using a combination of genetic and molecular approaches, we showed that GCN-2 kinase activity plays a central role in survival under nutrient stress and mediates lifespan extension conferred by dietary restriction (DR) or inhibition of the major nutrient-sensing pathway, the target of rapamycin (TOR). We also demonstrated that the GCN-2 and TOR signaling pathways converge on the PHA-4/FoxA transcription factor and its downstream target genes to ensure survival of the whole organism under a multitude of stress conditions, such as nutrient scarcity or environmental stresses. This is one step forward in the understanding of evolutionary conserved mechanisms that confer longevity and healthspan.