Economic Assessment in Resource-Constrained Systems: Individual-Level Simulation Model in Wet Age-Related Macular Degeneration and Diabetic Macular Oedema.

INTRODUCTION: Cost-effectiveness analyses typically ignore healthcare system resource constraints. Ophthalmology is affected by resource constraints because of increasing disease prevalence and the use of resource-intensive treatments. This study evaluated the impact of resource constraints on the cost-effectiveness of faricimab 6 mg, compared with aflibercept 2 mg and ranibizumab biosimilar 0.5 mg, for treating wet age-related macular degeneration (wAMD) or diabetic macular oedema (DMO) over a 5-year horizon. METHODS: A microsimulation model estimated the impact of resource constraints on patients visits, delays, costs and quality-adjusted life-year (QALY) losses due to treatment delays at a typical UK National Health Service eye hospital treating 1500 patients with wAMD and 500 patients with DMO. Patient characteristics, treatment regimens and treatment intervals were informed using published literature and expert opinion. Resource constraint was represented by limiting the number of available intravitreal injection appointments per week, with growing demand caused by rising disease prevalence. The model compared outcomes across three scenarios; each scenario involved treating all patients with one of the three treatments. RESULTS: Over 5 years, in a resource-constrained hospital, compared with aflibercept, faricimab use resulted in the avoidance of 12,596 delays, saved GBP/£15,108,609 in cost and avoided the loss of 60.06 QALYs. Compared with ranibizumab biosimilar, faricimab use resulted in the avoidance of 18,910 delays, incurred £2,069,088 extra cost and avoided the loss of 105.70 QALYs, resulting in an incremental cost-effectiveness ratio of £19,574/QALY. CONCLUSIONS: Accounting for resource constraints in health economic evaluation is crucial. Emerging therapies that are more durable and require less frequent clinic visits can reduce treatment delays, leading to improved QALY outcomes and reduced burden on healthcare systems. Faricimab reduced the number of delayed injections, leading to improved QALY outcomes for patients in a healthcare system with resource constraints. Faricimab is cost-saving when compared with aflibercept and cost-effective when compared with ranibizumab biosimilar.

Clinical Outcomes and Experiences with Prefilled Syringes Versus Vials for Intravitreal Administration of Anti-VEGF Treatments: A Systematic Review.

INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) agents have been the standard treatment for retinal diseases for almost two decades. These treatments are administered via intravitreal injection using single-use vials or prefilled syringes (PFS). In this systematic review, we evaluate health care resource use and clinical outcomes and experiences with PFS for intravitreal injection of anti-VEGF treatments. METHODS: MEDLINE, EMBASE, and The Cochrane Library were searched from January 1, 2015 to February 8, 2024 to identify literature reporting outcomes regarding procedural efficiency, health care resource use, patient and clinician experiences, and safety for currently approved anti-VEGFs (ranibizumab, aflibercept, brolucizumab) administered using PFS. Comparators were vial-based injections of the same anti-VEGFs. RESULTS: A total of 36 publications met the criteria for inclusion in the systematic literature review; the majority were non-randomized studies, with a small number of reviews, case series, survey studies, and opinion articles. Publications reported that preparation times were significantly shorter for PFS (40.3-57.9 s) versus vials (ranibizumab, 62.8-98.0 s; aflibercept, 71.9-79.5 s), with no differences in product stability between PFS and vials. Clinicians expressed a preference for PFS and thought PFS were faster, easier to use, and had increased safety versus vials. Publications consistently reported significantly lower rates of endophthalmitis per injection with PFS versus vials (ranibizumab PFS, 0-0.02%; aflibercept PFS, 0.01-0.02%; ranibizumab vial, 0.02-0.05%; aflibercept vial, 0.02-0.06%). Four publications reported increased rates of transient vision loss after aflibercept PFS injection versus vial-based injection. No publications reported outcomes regarding health care resource use or patient experiences. CONCLUSION: The available literature supports the increased procedural efficiency of PFS versus vial-based intravitreal injection of anti-VEGFs. PFS are positively perceived by clinicians and have a safety benefit in the form of a decreased risk of endophthalmitis versus vials.

Anti-vascular endothelial growth factor (VEGF) drugs, given by injection into the eye, are commonly used to treat diseases that affect the back of the eye (the retina). Anti-VEGF drugs are provided in small containers (vials) or in syringes that are already filled with the drug (prefilled syringes). When someone is treated with an anti-VEGF drug from a vial, the drug must first be taken from the vial using a needle and syringe, and then injected. When someone is treated with an anti-VEGF drug from a prefilled syringe, the drug is injected directly from the prefilled syringe, i.e., there are fewer steps involved when a prefilled syringe is used. We searched the medical literature to see if there were differences in clinical outcomes and experiences between prefilled syringes and vials when used to inject anti-VEGF drugs. Clinicians spent about 50% less time getting ready for injections when prefilled syringes were used than when vials were used. Clinicians also preferred to use prefilled syringes than vials for injecting anti-VEGF drugs. Clinicians reported that prefilled syringes were easier to use, faster, and safer than vials. Patients who were given injections from prefilled syringes had a lower rate of infection of the inside of the eye (endophthalmitis) than patients who were given injections from vials. These results indicate that using prefilled syringes for injecting drugs into the eye can improve efficiency at ophthalmology clinics and improve safety for patients.

An eye on equity: faricimab-driven health equity improvements in diabetic macular oedema using a distributional cost-effectiveness analysis from a UK societal perspective.

BACKGROUND/OBJECTIVES: Diabetic macular oedema (DMO) is a leading cause of blindness in developed countries, with significant disease burden associated with socio-economic deprivation. Distributional cost-effectiveness analysis (DCEA) allows evaluation of health equity impacts of interventions, estimation of how health outcomes and costs are distributed in the population, and assessments of potential trade-offs between health maximisation and equity. We conducted an aggregate DCEA to determine the equity impact of faricimab. METHODS: Data on health outcomes and costs were derived from a cost-effectiveness model of faricimab compared with ranibizumab, aflibercept and off-label bevacizumab using a societal perspective in the base case and a healthcare payer perspective in scenario analysis. Health gains and health opportunity costs were distributed across socio-economic subgroups. Health and equity impacts, measured using the Atkinson inequality index, were assessed visually on an equity-efficiency impact plane and combined into a measure of societal welfare. RESULTS: At an opportunity cost threshold of £20,000/quality-adjusted life year (QALY), faricimab displayed an increase in net health benefits against all comparators and was found to improve equity. The equity impact increased the greater the concerns for reducing health inequalities over maximising population health. Using a healthcare payer perspective, faricimab was equity improving in most scenarios. CONCLUSIONS: Long-acting therapies with fewer injections, such as faricimab, may reduce costs, improve health outcomes and increase health equity. Extended economic evaluation frameworks capturing additional value elements, such as DCEA, enable a more comprehensive valuation of interventions, which is of relevance to decision-makers, healthcare professionals and patients.

Synthetic studies on the reverse antibiotic natural products, the nybomycins.

Antimicrobial resistance (AMR) is a serious issue that could have severe consequences if steps are not taken. The nybomycin natural products have the potential to extend the clinical efficacy of the marketed fluoroquinolone class of antibiotics through a 'reverse antibiotic' approach. However, only very limited structure-activity relationships are known for these fascinating compounds, in part due to challenges with their synthesis. Here we report a new scalable and robust synthetic route to the nybomycin natural products to aid in the development of this series. Through this synthesis, we report the antibiotic activity of novel analogues of this family confirming the selectivity for fluoroquinolone resistant bacteria and potential future opportunities for further optimisation.

Ascent exhalations of Antarctic fur seals: a behavioural adaptation for breath-hold diving?

Novel observations collected from video, acoustic and conductivity sensors showed that Antarctic fur seals consistently exhale during the last 50-85% of ascent from all dives (10-160 m, n > 8000 dives from 50 seals). The depth of initial bubble emission was best predicted by maximum dive depth, suggesting an underlying physical mechanism. Bubble sound intensity recorded from one seal followed predictions of a simple model based on venting expanding lung air with decreasing pressure. Comparison of air release between dives, together with lack of variation in intensity of thrusting movement during initial descent regardless of ultimate dive depth, suggested that inhaled diving lung volume was constant for all dives. The thrusting intensity in the final phase of ascent was greater for dives in which ascent exhalation began at a greater depth, suggesting an energetic cost to this behaviour, probably as a result of loss of buoyancy from reduced lung volume. These results suggest that fur seals descend with full lung air stores, and thus face the physiological consequences of pressure at depth. We suggest that these regular and predictable ascent exhalations could function to reduce the potential for a precipitous drop in blood oxygen that would result in shallow-water blackout.