UNASSIGNED: This economic evaluation of axicabtagene ciloleucel (axi-cel) versus previous standard of care (SOC; salvage chemotherapy followed by high-dose therapy with autologous stem cell rescue) in the second line (2L) large B-cell lymphoma population is an update of previous economic models that contained immature survival data.
UNASSIGNED: This analysis is based on primary overall survival (OS) ZUMA-7 clinical trial data (median follow-up of 47.2 months), from a United States (US) payer perspective, with a model time horizon of 50 years. Mixture cure models were used to extrapolate updated survival data; subsequent treatment data and costs were updated. Patients who remained in the event-free survival state by 5 years were assumed to have achieved long-term remission and not require subsequent treatment.
UNASSIGNED: Substantial survival and quality of life benefits were observed despite 57% of patients in the SOC arm receiving subsequent cellular therapy: median model-projected (ZUMA-7 trial Kaplan-Meier estimated) OS was 78 months (median not reached) for axi-cel versus 25 months (31 months) for SOC, resulting in incremental quality-adjusted life year (QALY) difference of 1.63 in favor of axi-cel. Incrementally higher subsequent treatment costs were observed in the SOC arm due to substantial crossover to cellular therapies, thus, when considering the generally accepted willingness to pay threshold of $150,000 per QALY in the US, axi-cel was cost-effective with an incremental cost-effectiveness ratio of $98,040 per QALY.
UNASSIGNED: Results remained consistent across a wide range of sensitivity and scenario analysis, including a crossover adjusted analysis, suggesting that the mature OS data has significantly reduced the uncertainty of axi-cel\'s cost-effectiveness in the 2L setting in the US. Deferring treatment with CAR T therapies after attempting a path to transplant may result in excess mortality, lower quality of life and would be an inefficient use of resources relative to 2L axi-cel.

BACKGROUND: Mediterranean diets (MedDiets) are linked to substantial health benefits. However, there is also growing evidence that the intensification of food production over the last 60 years has resulted in nutritionally relevant changes in the composition of foods that may augment the health benefits of MedDiets.
OBJECTIVE: To synthesize, summarize, and critically evaluate the currently available evidence for changes in food composition resulting from agricultural intensification practices and their potential impact on the health benefits of MedDiets.
METHODS: We summarized/synthesized information from (i) systematic literature reviews/meta-analyses and more recently published articles on composition differences between conventional and organic foods, (ii) desk studies which compared food composition data from before and after agricultural intensification, (iii) recent retail and farm surveys and/or factorial field experiments that identified specific agronomic practices responsible for nutritionally relevant changes in food composition, and (iv) a recent systematic literature review and a small number of subsequently published observational and dietary intervention studies that investigated the potential health impacts of changes in food composition resulting from agricultural intensification.
CONCLUSIONS: There has been growing evidence that the intensification of food production has resulted in (i) lower concentrations of nutritionally desirable compounds (e.g., phenolics, certain vitamins, mineral micronutrients including Se, Zn, and omega-3 fatty acids, α-tocopherol) and/or (ii) higher concentrations of nutritionally undesirable or toxic compounds (pesticide residues, cadmium, omega-6 fatty acids) in many of the foods (including wholegrain cereals, fruit and vegetables, olive oil, dairy products and meat from small ruminants, and fish) that are thought to contribute to the health benefits associated with MedDiets. The evidence for negative health impacts of consuming foods from intensified conventional production systems has also increased but is still limited and based primarily on evidence from observational studies. Limitations and gaps in the current evidence base are discussed. Conclusions: There is now substantial evidence that the intensification of agricultural food production has resulted in a decline in the nutritional quality of many of the foods that are recognized to contribute to the positive health impacts associated with adhering to traditional MedDiets. Further research is needed to quantify to what extent this decline augments the positive health impacts of adhering to a traditional MedDiet.

UNASSIGNED: Thailand\'s national smoking cessation services (FAH-SAI clinics) were founded in 2010. A cost-effectiveness analysis (CEA) is needed to inform policymakers of the allocation and prioritization of the limited budget to maximize the value for money of reimbursing these services. Chronic obstructive pulmonary disease (COPD) patients would benefit from smoking cessation services. Therefore, this study aimed to assess the cost-effectiveness of these multidisciplinary services compared to the usual care among COPD patients in Thailand from a societal perspective.
UNASSIGNED: We conducted a CEA from a societal perspective using a Markov model to simulate lifetime costs and quality-adjusted life years (QALYs) gained by each smoking cessation intervention over the patient\'s lifetime. We derived the effectiveness of the smoking cessation services from a multicenter, longitudinal study of smoking cessation services in Thailand and estimated the natural quit rate, transition probabilities, health utility, and cost data from the published literature. Costs and outcomes were discounted at 3%. Sensitivity analyses were performed.
UNASSIGNED: Compared to the usual care, FAH-SAI clinics were associated with higher costs (4,207 THB (US$133)) and improved QALYs (0.11), with an incremental cost-effectiveness ratio of 37,675 THB/QALY (US$1,187/QALY). The effectiveness of FAH-SAI clinics was a key driver of the cost-effectiveness results. At the willingness-to-pay (WTP) threshold of 160,000 THB (US$5,042) per QALY gained, the probability of being cost-effective was 96.5%.
UNASSIGNED: FAH-SAI clinics were cost-effective under Thailand\'s WTP threshold. Our results could inform policymakers in allocating resources to support smoking cessation services for COPD patients in Thailand.

UNASSIGNED: There is currently a need for additional diagnostic information to help guide treatment decisions and to properly determine the best treatment pathway for patients identified with indeterminate pulmonary nodules (IPNs). The aim of this study was to demonstrate the incremental cost-effectiveness of LungLB compared to the current clinical diagnostic pathway (CDP) in the management of patients with IPNs, from a US payer\'s perspective.
UNASSIGNED: A decision tree and Markov model hybrid was chosen from a payer perspective in the US setting, based on published literature, to assess the incremental cost-effectiveness of LungLB compared to the current CDP in the management of patients with IPNs. Primary endpoints of the analysis include expected costs, life years (LYs), and quality-adjusted life years (QALYs) for each arm of the model, as well as an incremental cost-effectiveness ratio (ICER), which is calculated as the incremental costs per QALY, and net monetary benefit (NMB).
UNASSIGNED: We find that, with the inclusion of LungLB to the current CDP diagnostic pathway, expected LYs over the typical patient\'s lifespan increase by 0.07 years and QALYs increase by 0.06. The average patient in the CDP arm will pay approximately $44,310 over their lifespan, while a patient in the LungLB arm will pay $48,492, resulting in a difference of $4,182. The differentials between the CDP and LungLB arms of the model in costs and QALYs yield an ICER of $75,740 per QALY and an incremental NMB of $1,339.
UNASSIGNED: This analysis provides evidence that LungLB, in conjunction with CDP, is a cost-effective alternative compared to the current CDP alone in a US setting for individuals with IPNs.

UNASSIGNED: Left atrial ablation to obtain pulmonary vein isolation (PVI) for the treatment of atrial fibrillation (AF) is a technologically intensive procedure utilizing innovative and continually improving technology. Changes in the technology utilized for PVI can in turn lead to changes in procedure costs. Because of the proximity of the esophagus to the posterior wall of the left atrium, various technologies have been utilized to protect against thermal injury during ablation. The impact on hospital costs during PVI ablation from utilization of different technologies for esophageal protection during ablation has not previously been evaluated.
UNASSIGNED: To compare the costs of active esophageal cooling to luminal esophageal temperature (LET) monitoring during left atrial ablation.
UNASSIGNED: We performed a time-driven activity-based costing (TDABC) analysis to determine costs for PVI procedures. Published data and literature review were utilized to determine differences in procedure time and same-day discharge rates using different esophageal protection technologies and to determine the cost impacts of same-day discharge versus overnight hospitalization after PVI procedures. The total costs were then compared between cases using active esophageal cooling to those using LET monitoring.
UNASSIGNED: The effect of implementing active esophageal cooling was associated with up to a 24.7% reduction in mean total procedure time, and an 18% increase in same-day discharge rate. TDABC analysis identified a $681 reduction in procedure costs associated with the use of active esophageal cooling after including the cost of the esophageal cooling device. Factoring in the 18% increase in same-day discharge resulted in an increased cost savings of $2,135 per procedure.
UNASSIGNED: The use of active esophageal cooling is associated with significant cost-savings when compared to traditional LET monitoring, even after accounting for the additional cost of the cooling device. These savings originate from a per-patient procedural time savings and a per-population improvement in same-day discharge rate.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease with 30% mortality from heart failure (HF) in the first year of life, but the cause of early HF remains unknown. Induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CM) from patients with HLHS showed that early HF is associated with increased apoptosis, mitochondrial respiration defects, and redox stress from abnormal mitochondrial permeability transition pore (mPTP) opening and failed antioxidant response. In contrast, iPSC-CM from patients without early HF showed normal respiration with elevated antioxidant response. Single-cell transcriptomics confirmed that early HF is associated with mitochondrial dysfunction accompanied with endoplasmic reticulum (ER) stress. These findings indicate that uncompensated oxidative stress underlies early HF in HLHS. Importantly, mitochondrial respiration defects, oxidative stress, and apoptosis were rescued by treatment with sildenafil to inhibit mPTP opening or TUDCA to suppress ER stress. Together these findings point to the potential use of patient iPSC-CM for modeling clinical heart failure and the development of therapeutics.

OBJECTIVE: The Novel Coronavirus (COVID-19) has infected over two hundred million worldwide and caused 4.4 million of deaths as of August 2021. Vaccines were quickly developed to address the pandemic. We sought to analyze the cost-effectiveness and budget impact of a non-specified vaccine for COVID-19.
METHODS: We constructed a Markov model of COVID-19 infections using a susceptible-exposed-infected-recovered structure over a 1-year time horizon from a U.S. healthcare sector perspective. The model consisted of two arms: do nothing and COVID-19 vaccine. Hospitalization and mortality rates were calibrated to U.S. COVID-19 reports as of November 2020. We performed economic calculations of costs in 2020 U.S. dollars and effectiveness in units of quality-adjusted life years (QALYs) to measure the budget impact and incremental cost-effectiveness at a $100,000/QALY threshold.
RESULTS: Vaccines have a high probability of reducing healthcare costs and increasing QALYs compared to doing nothing. Simulations showed reductions in hospital days and mortality by more than 50%. Even though this represents a major U.S. investment, the budget impacts of these technologies could save program costs by up to 60% or more if uptake is high.
CONCLUSIONS: The economic evaluation draws on the reported values of the clinical benefits of COVID-19 vaccines, although we do not currently have long-term conclusive data about COVID-19 vaccine efficacies.
CONCLUSIONS: Spending on vaccines to mitigate COVID-19 infections offer high-value potential that society should consider. Unusually high uptake in vaccines in a short amount of time could result in unprecedented budget impacts to government and commercial payers. Governments should focus on expanding health system infrastructure and subsidizing payer coverage to deliver these vaccines efficiently.

UNASSIGNED: Hemophilia A is the second most common bleeding disorder causing patients to have lifelong follow-up and treatment. Despite being a rare disease, hemophilia A has a high economic burden on individuals and the public. The purpose of this study was to estimate the total disease cost of hemophilia A in Turkey.
UNASSIGNED: Data used in this analysis were collected through literature review, including studies conducted in Turkey in December 2018. A disease burden analysis was performed by modeling hemophilia A-related costs among patients, their relatives, and the social security system. Two expert panels were held to evaluate real-world data sources and to provide further information. All direct medical and non-medical costs were calculated annually from the Social Security Institution of the Republic of Turkey perspective, while indirect costs were estimated from the patient and community perspective.
UNASSIGNED: For the calendar year of 2018, the number of hemophilia A patients in Turkey were estimated to be 5,055, with an average weight of 64.7 kg. The average annual direct medical, direct non-medical, and indirect costs of hemophilia A were calculated as €93,268 ($109,286; ₺502,717), €2,533 ($2,968; ₺13,655), and €7,957 ($9,323; ₺42,888) per patient, respectively, with a total annual cost of €103,759 ($121,578; ₺559,259). For the management of patients with inhibitors (4.9%), the average annual total cost was calculated to be €325,439 ($381,330; ₺1,754,117) per patient. The total annual disease burden of hemophilia A in 2018 was estimated to be about €524 million ($614 million; ₺2.82 billion), which corresponded to 1.6% of the total health expenditure in Turkey.
UNASSIGNED: The most important reason hemophilia A has a significant economic burden in Turkey is that replacement therapy is expensive. The major cost contributor was identified as factor replacement therapy. With inhibitor development, the average annual cost increased more than 3-fold.

UNASSIGNED: Glioblastoma is the most common primary brain tumor in adults. Standard of care includes maximal surgical resection of the tumor followed by concurrent chemotherapy and radiation. The treatment of glioblastoma must account for an increased disease severity and treatment intensity compared to other cancers which place a significant cost burden on the patient and health system. Cost assessments of glioblastoma treatment have been sparse in comparison to other solid cancer subtypes. This study evaluates all currently available cost literature with an emphasis on the modern treatment paradigm to properly assess the economic implications of this disease.
UNASSIGNED: A critical review of 21 studies from 13 different countries measuring direct costs related to glioblastoma management was performed. Evaluated data included itemized costs, total costs of treatment regimens from diagnosis until death, the cost of second-line care after recurrence, and the incremental costs and cost-effectiveness of emerging therapies.
UNASSIGNED: The average cost of a craniotomy was $10,042 across studies. Imaging for the duration of glioblastoma care had a mean cost of $2,788 ± 3,719. Studies examined different combinations of treatment modalities. Utilization of the modern treatment paradigm led to survival of 16.3 months across studies and had a mean cost of $62,602. Surgery for the recurrent disease had an average cost of $27,442 ± 18,992.
UNASSIGNED: Direct cost estimates for glioblastoma varied substantially between institutions and countries and often failed to uniformly describe direct cost estimates associated with care for glioblastoma. The limitations of these studies make a true economic assessment of standards of care, costs of recurrence, and incremental costs associated with adjunctive therapy uncertain.

UNASSIGNED: There is wide variation in opioid prescribing patterns after common surgical procedures. This study examines outcomes for beneficiaries undergoing hospital outpatient department (HOPD) procedures using liposomal bupivacaine (LB) for control of post-surgical pain. As a non-opioid surgical analgesic, LB may afford beneficial outcomes for reducing subsequent opioid use and improving post-surgical service use outcomes.
UNASSIGNED: This retrospective cohort comparison study analyzed 100% Medicare claims data from 2014-2019. HOPD claims were matched to approximately 100 of the most common surgical procedures where LB was utilized. Within these procedures, a one-to-many, with replacement propensity score matching model was used to control for possible selection bias. By procedure, those claims which were identified as using LB for control of post-surgical pain were matched to those not receiving LB. Outcomes were the probability of a subsequent Part D opioid prescription fill, emergency department (ED) visit, and short-term acute care hospital admission.
UNASSIGNED: Higher provider use rates of LB are significantly correlated with a decrease in post-HOPD opioid use and a reduction in post-operative ED visits. For each 10% increase in LB use rate by a given provider, Part D opioid events by Day 30 decreased by 2.6 percentage points and by 2.1 percentage points by day 90 (p < .01). Similarly, for each 10% increase in provider LB use rate, there is a 0.4 percentage point reduction in post-operative ED use by day 30 (p < .01) and a 0.3 percentage point reduction by day 90 (p < .05).
UNASSIGNED: Part D data only indicate that a prescription was filled, not whether the drug was taken.
UNASSIGNED: Increased provider use of LB is correlated with improved patient outcomes in real-world provider experience with the Medicare population for many outpatient procedures. Policies that support increased provider use of LB should reduce reliance on opioid drugs for post-surgical pain management.