UNASSIGNED: Research relating to Total Hip Arthroplasty (THA) has found the anterior-based muscle-sparing (ABMS) approach improves both intraoperative and postoperative outcomes when compared to other THA approaches. This study compares the costs and outcomes of the ABMS approach and standard of care (SOC) to determine the relative cost-effectiveness.
UNASSIGNED: A decision-analytic model was utilized to estimate intraoperative outcomes (i.e. length of procedure, length of stay (LOS), and transfusion rates) and 90-day postoperative complications (deep infection, periprosthetic fracture, and dislocation). Data relating to postoperative complications, intraoperative outcomes, and costs (adjusted to 2023 USD) were obtained from the literature. Model results were presented as incremental costs and complications avoided using a willingness-to-pay threshold of $100,000. We conducted both one-way sensitivity analysis (OWSA), varying each parameter individually within a specific range, and probabilistic sensitivity analysis (PSA) where parameters were varied simultaneously. In scenario analysis, ABMS was also compared to the posterior approach (PA) and direct anterior approach (DAA) individually.
UNASSIGNED: ABMS THA was found to have superior results compared to SOC THA over a 90-day time horizon since it decreased major complications by 0.00186 per patient and cost by $3,851 per patient. The PSA found the ABMS approach dominates SOC and is cost-effective in approximately 98.29% and 100% of 10,000 iterations, respectively. Comparing ABMS with only PA procedures increased cost savings per patient to $4,766 while it decreased to $3,242 when comparing ABMS to only DAA procedures. Length of procedure, LOS, and discharge disposition were the main cost drivers.
UNASSIGNED: This analysis demonstrates the ABMS approach for THA is a cost-effective technique when compared to PA and DAA, which may provide an opportunity for cost savings to the healthcare system.

The Vaccines Task Force was established by the UK government in March 2020, with the objective of securing early access to effective COVID-19 vaccines for the UK population and internationally. The VTF was successful in securing the earliest access to the Oxford/Astra Zeneca and Pfizer/BioNTech vaccines, allowing the UK to be the first country in the world to deploy an approved COVID-19 vaccine. The VTF also played a critical role in supporting efforts to distribute vaccines globally, as one of COVAX\'s earliest and largest donors. This article presents the perspectives of senior members of the VTF on the features of the task force model which enabled this success, and considers lessons for when and how a similar approach should be applied to other public health and public policy challenges. We seek to identify principles for mission led government, and implications for how the structure and apparatus of governance can be organised to support this, including the application of the Task Force model where appropriate.

UNASSIGNED: Fruquintinib is a selective small molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3 recently approved in the United States (US) for the treatment of adult patients with metastatic colorectal cancer (CRC) who have previously been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type and medically appropriate, anti-epidermal growth factor receptor therapy. This study aimed to estimate the 5-year budget impact of fruquintinib from a US payer perspective (commercial and Medicare).
UNASSIGNED: A budget impact model was developed to compare two scenarios: a reference scenario in which patients received regorafenib, trifluridine/tipiracil, or trifluridine/tipiracil with bevacizumab and an alternative scenario in which patients received reference scenario treatments or fruquintinib. Market shares were evenly divided across available options. A 5-year time horizon and a hypothetical health plan of 1 million members was assumed. The model included epidemiological inputs to estimate the eligible population; clinical inputs for treatment duration, progression-free survival, overall survival, and adverse event (AE) frequency; and cost inputs for treatment, AEs, disease management, subsequent therapy, and terminal care costs. Budget impact was reported as total, per member per year (PMPY), and per member per month (PMPM).
UNASSIGNED: The model estimated an eligible population of 194 patients (39 per year) over 5 years. In the base case, the estimated 5-year budget impact of fruquintinib was $4,077,073 ($0.82 PMPY and 0.07 PMPM) for a commercial health plan. During the first year, the estimated budget impact was $627,570 ($0.63 PMPY and 0.05 PMPM). Results were robust across sensitivity analyses. PMPM costs from the Medicare perspective were greater than the base-case (commercial) ($0.17 vs. $0.07) due to higher incidence of CRC in that population.
UNASSIGNED: Fruquintinib is associated with a low budget impact for payers based on proposed thresholds in the US.
Fruquintinib is a treatment for metastatic colorectal cancer that has progressed after or not responded to multiple guideline-recommended therapies. This budget impact analysis was conducted to estimate the added costs a health plan would incur over a 5-year period if it chose to cover this therapy. The analysis found that the per plan member per month cost of covering fruquintinib was $0.07 for a United States commercial health plan and $0.17 for Medicare.

UNASSIGNED: Nearly one in ten individuals in South-East Asia are estimated to be affected by chronic kidney disease (CKD). The burden of end-stage kidney disease is significant and can be heavy on the healthcare system. The recent EMPA-KIDNEY trial demonstrated a significant reduction in the risk of kidney disease progression or cardiovascular death in patients with CKD with a broad range of kidney function using add-on empagliflozin versus standard of care (SoC) alone. The objective of this study was to estimate the economic benefit of empagliflozin for patients with CKD in Malaysia, Thailand and Vietnam.
UNASSIGNED: An individual patient level simulation model with an annual cycle that estimates the progression of kidney function and associated risk-factors was employed. Local costs and mortality rates were estimated from a wide range of published literature. A healthcare perspective was used over a 50-year time horizon.
UNASSIGNED: The use of add-on empagliflozin versus SoC alone was found to be cost-saving in Malaysia and Thailand and cost-effective (ICER: 77,838,407 Vietnam Dong/QALY vs. a willingness to pay threshold of 96,890,026/QALY) in Vietnam. The bulk of the costs avoided over a lifetime is derived from the prevention or delay of dialysis initiation or kidney transplant - the cost offsets were nearly twice the additional treatment cost. The results were similar in patients with and without diabetes and across broad range of albuminuria.
UNASSIGNED: The use of add-on empagliflozin in a broad population of patients with CKD is expected to be cost-saving in Malaysia and Thailand and cost-effective in Vietnam and will help alleviate the increasing burden of CKD in the region.

UNASSIGNED: To compare the cost, healthcare utilization, and outcomes between skin and serum-specific IgE (sIgE) allergy testing.
UNASSIGNED: This retrospective cohort study used IBM® MarketScan claims data, from which commercially insured individuals who initiated allergy testing between January 1 and December 31, 2018 with at least 12 months of enrollment data before and after index testing date were included. Cost of allergy testing per patient was estimated by testing pattern: skin only, sIgE only, or both. Multivariable linear regression was used to compare healthcare utilization and outcomes, including office visits, allergy and asthma-related prescriptions, and emergency department (ED) and urgent care (UC) visits between skin and sIgE testing at 1-year post testing (α = 0.05).
UNASSIGNED: The cohort included 168,862 patients, with a mean (SD) age of 30.8 (19.5) years; 100,666 (59.7%) were female. Over half of patients (56.4%, n = 95,179) had skin only testing, followed by 57,291 patients with sIgE only testing and 16,212 patients with both testing. The average cost of allergy testing per person in the first year was $430 (95% CI $426-433) in patients with skin only testing, $187 (95% CI $183-190) in patients with sIgE only testing, and $532 (95% CI $522-542) in patients with both testing. At 1-year follow-up post testing, there were slight increases in allergy and asthma-related prescriptions, and notable decreases in ED visits by 17.0-17.4% and in UC visits by 10.9-12.6% for all groups (all p < 0.01). Patients with sIgE-only testing had 3.2 fewer allergist/immunologist visits than patients with skin-only testing at 1-year follow-up (p < 0.001). Their healthcare utilization and outcomes were otherwise comparable.
UNASSIGNED: Allergy testing, regardless of the testing method used, is associated with decreases in ED and UC visits at 1-year follow-up. sIgE allergy testing is associated with lower testing cost and fewer allergist/immunologist visits, compared to skin testing.

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Salmonella infection entails a cascade of attacks and defence measures. After breaching the intestinal epithelial barrier, Salmonella is phagocytosed by macrophages, where the bacteria encounter multiple stresses, to which it employs relevant countermeasures. Our study shows that, in Salmonella, the polyamine spermidine activates a stress response mechanism by regulating critical antioxidant genes. Salmonella Typhimurium mutants for spermidine transport and synthesis cannot mount an antioxidative response, resulting in high intracellular ROS levels. These mutants are also compromised in their ability to be phagocytosed by macrophages. Furthermore, it regulates a novel enzyme in Salmonella, Glutathionyl-spermidine synthetase (GspSA), which prevents the oxidation of proteins in E. coli. Moreover, the spermidine mutants and the GspSA mutant show significantly reduced survival in the presence of hydrogen peroxide in vitro and reduced organ burden in the mouse model of Salmonella infection. Conversely, in macrophages isolated from gp91phox-/- mice, we observed a rescue in the attenuated fold proliferation previously observed upon infection. We found that Salmonella upregulates polyamine biosynthesis in the host through its effectors from SPI-1 and SPI-2, which addresses the attenuated proliferation observed in spermidine transport mutants. Thus, inhibition of this pathway in the host abrogates the proliferation of Salmonella Typhimurium in macrophages. From a therapeutic perspective, inhibiting host polyamine biosynthesis using an FDA-approved chemopreventive drug, D, L-α-difluoromethylornithine (DFMO), reduces Salmonella colonisation and tissue damage in the mouse model of infection while enhancing the survival of infected mice. Therefore, our work provides a mechanistic insight into the critical role of spermidine in stress resistance of Salmonella. It also reveals a bacterial strategy in modulating host metabolism to promote their intracellular survival and shows the potential of DFMO to curb Salmonella infection.

UNASSIGNED: Pembrolizumab plus lenvatinib was recently approved for the treatment of advanced or recurrent endometrial carcinoma in women with disease progression on or following prior treatment with a platinum‑containing therapy in any setting, and who are not candidates for curative surgery or radiation (KEYNOTE-775/Study-309; NCT03517449). The objective was to assess the cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy from a Swedish healthcare perspective.
UNASSIGNED: A lifetime partitioned-survival model with three health states (progression free, progressed disease, death) was constructed. Chemotherapy was represented by paclitaxel or doxorubicin. Overall survival, progression-free survival, time on treatment, and utility data were obtained from KEYNOTE-775 (database lock: March 1, 2022). Costs (in 2020 Swedish Krona [SEK]) included drug acquisition and administration, health state, end of life, adverse event management, subsequent treatment, and societal (scenario analysis). Outcomes were calculated as quality-adjusted life-years (QALY) and life-years. Model results were presented as incremental cost-effectiveness ratios for all-comers, patients with proficient mismatch repair tumors, and deficient mismatch repair tumors. Deterministic and probabilistic sensitivity analyses were conducted.
UNASSIGNED: Pembrolizumab plus lenvatinib is a cost-effective treatment when compared with chemotherapy, with estimated deterministic and probabilistic incremental cost-effectiveness ratios of SEK 795,712 and 819,757 per QALY gained. Pembrolizumab plus lenvatinib was associated with a large incremental QALY and life-year gain per person versus chemotherapy over the model time horizon (1.49 and 1.76).
UNASSIGNED: Time-to-event data were incomplete and semiparametric and parametric curves were utilized for lifetime extrapolation. Willingness-to-pay thresholds, costs, and utility weights vary by country, which would vary the treatment\'s cost effectiveness in different countries.
UNASSIGNED: This partitioned survival analysis suggests that pembrolizumab plus lenvatinib is cost effective compared with chemotherapy in Sweden for women with advanced or recurrent endometrial carcinoma following previous systemic therapy. Results were robust to mismatch repair status and to changes in parameters/assumptions.

UNASSIGNED: Patients with previously treated microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) tumours have limited chemotherapeutic treatment options. Pembrolizumab received approval from the EMA in 2022 for the treatment of colorectal, endometrial, gastric, small intestine, and biliary MSI-H/dMMR tumour types. This approval was supported by data from the KEYNOTE-164 and KEYNOTE-158 clinical trials. This study evaluated the cost-effectiveness of pembrolizumab compared with standard of care (SoC) for previously treated MSI-H/dMMR solid tumours in line with the approved EMA label from a UK healthcare payer perspective.
UNASSIGNED: A multi-tumour partitioned survival model was built consisting of pre-progression, progressed disease, and dead health states. Pembrolizumab survival outcomes were extrapolated using Bayesian hierarchical models (BHMs) fitted to pooled data from KEYNOTE-164 and KEYNOTE-158. Comparator outcomes were informed by published sources. Tumour sites were modelled independently and then combined, weighted by tumour site distribution. A SoC comparator was used to formulate the overall cost-effectiveness result with pembrolizumab as the intervention. SoC comprised a weighted average of the comparators by tumour site based on market share. Drug acquisition, administration, adverse events, monitoring, subsequent treatment, end-of-life costs, and testing costs were included. Sensitivity and scenario analyses were performed, including modelling pembrolizumab efficacy using standard parametric survival models.
UNASSIGNED: Pembrolizumab, at list price, was associated with £129,469 in total costs, 8.30 LYs, and 3.88 QALYs across the pooled tumour sites. SoC was associated with £28,222 in total costs, 1.14 LYs, and 0.72 QALYs across the pooled tumour sites. This yields an incremental cost-effectiveness ratio (ICER) of £32,085 per QALY. Results were robust to sensitivity and scenario analyses.
UNASSIGNED: This model demonstrates pembrolizumab provides a valuable new alternative therapy for UK patients with MSH-H/dMMR cancer at the cost of £32,085 per QALY, with confidential discounts anticipated to improve cost-effectiveness further.

UNASSIGNED: This study aimed to evaluate the cost-effectiveness of lung cancer screening (LCS) with volume-based low-dose computed tomography (CT) versus no screening for an asymptomatic high-risk population in the United Kingdom (UK), utilising the long-term insights provided by the NELSON study, the largest European randomized control trial investigating LCS.
UNASSIGNED: A cost-effectiveness analysis was conducted using a decision tree and a state-transition Markov model to simulate the identification, diagnosis, and treatments for a lung cancer high-risk population, from a UK National Health Service (NHS) perspective. Eligible participants underwent annual volume CT screening and were compared to a cohort without the option of screening. Screen-detected lung cancers, costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) were predicted.
UNASSIGNED: Annual volume CT screening of 1.3 million eligible participants resulted in 96,474 more lung cancer cases detected in early stage, and 73,825 fewer cases in late stage, leading to 53,732 premature lung cancer deaths averted and 421,647 QALYs gained, compared to no screening. The ICER was £5,455 per QALY. These estimates were robust in sensitivity analyses.
UNASSIGNED: Lack of long-term survival data for lung cancer patients; deficiency in rigorous micro-costing studies to establish detailed treatment costs inputs for lung cancer patients.
UNASSIGNED: Annual LCS with volume-based low-dose CT for a high-risk asymptomatic population is cost-effective in the UK, at a threshold of £20,000 per QALY, representing an efficient use of NHS resources with substantially improved outcomes for lung cancer patients, as well as additional societal and economic benefits for society as a whole. These findings advocate evidence-based decisions for the potential implementation of a nationwide LCS in the UK.