Cost-effective Treatment Strategy Research Articles

Deep caries detection using deep learning: from dataset acquisition to detection.

The study aims to address the global burden of dental caries, a highly prevalent disease affecting billions of individuals, including both children and adults. Recognizing the significant health challenges posed by untreated dental caries, particularly in low- and middle-income countries, our goal is to improve early-stage detection. Though effective, traditional diagnostic methods, such as bitewing radiography, have limitations in detecting early lesions. By leveraging Artificial Intelligence (AI), we aim to enhance the accuracy and efficiency of caries detection, offering a transformative approach to dental diagnostics. This study proposes a novel deep learning-based approach for dental caries detection using the latest models, i.e., YOLOv7, YOLOv8, and YOLOv9. Trained on a dataset of over 3,200 images, the models address the shortcomings of existing detection methods and provide an automated solution to improve diagnostic accuracy. The YOLOv7 model achieved a mean Average Precision (mAP) at 0.5 Intersection over Union (IoU) of 0.721, while YOLOv9 attained a mAP@50 IoU of 0.832. Notably, YOLOv8 outperformed both, with a mAP@0.5 of 0.982. This demonstrates robust detection capabilities across multiple categories, including caries," "Deep Caries," and "Exclusion." This high level of accuracy and efficiency highlights the potential of integrating AI-driven systems into clinical workflows, improving diagnostic capabilities, reducing healthcare costs, and contributing to better patient outcomes, especially in resource-constrained environments. Integrating these latest YOLO advanced AI models into dental diagnostics could transform the landscape of caries detection. Enhancing early-stage diagnosis accuracy can lead to more precise and cost-effective treatment strategies, with significant implications for improving patient outcomes, particularly in low-resource settings where traditional diagnostic capabilities are often limited.

A propensity score-matched cost-effectiveness analysis of magnetic resonance-guided laser interstitial thermal therapy versus craniotomy for brain tumor radiation necrosis.

Radiation necrosis is becoming an increasingly prevalent complication in patients with brain tumors given the growing utility of stereotactic radiosurgery in modern treatment paradigms. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a new minimally invasive modality that has exhibited an efficacy comparable to craniotomy in treating radiation necrosis. No studies to date have compared their cost-effectiveness despite the significant additional expenses associated with MRgLITT use. This study aimed to evaluate the cost-effectiveness of MRgLITT versus craniotomy in patients with comparable presentations of radiation necrosis. The National Inpatient Sample (NIS) was queried from 2011 to 2020 for patients with radiation necrosis and treated using craniotomy or MRgLITT. Admission charges and costs were inflation adjusted to 2020 $US. Surgical cohorts were propensity score-matched according to demographic, clinical, and admission characteristics. Multivariable linear and logistic regression analyses identified associations between type of intervention and outcomes. A semi-Markov model was created to simulate treatment with craniotomy versus MRgLITT. Cost, transition probabilities, and health state utilities were derived from the NIS, individual patient outcomes from multiple institutions, and prospectively collected quality-of-life data from a single institution and verified against other studies. Monte Carlo simulation and probabilistic sensitivity analysis were used to evaluate the cost-effectiveness between the two modalities. In the designated study period, 2869 patients had been admitted with brain tumor radiation necrosis and were managed with neurosurgical intervention. After propensity score matching, MRgLITT, relative to craniotomy, was independently associated with a shorter length of stay (LOS; β = -1.81, p = 0.002), lower odds of complications (OR 0.18, p = 0.033), and higher odds of home discharge (OR 3.05, p = 0.041), but there was no difference in total admission costs between the two modalities (β = $6229, p = 0.081). On Monte Carlo simulation, patients treated with MRgLITT had a lower probability of disease (radiation necrosis or tumor) recurrence (13.5% vs 22.0%, p < 0.001) but an equivalent mortality risk (22.8% vs 22.3%, p = 0.429) compared to the patients treated with craniotomy at the 1-year follow-up. Over a 4-year time horizon, MRgLITT had an incremental cost of -$25,685 and incremental effectiveness of 0.14 quality-adjusted life-year (QALY), resulting in an incremental cost-effectiveness ratio of -$183,464 per QALY relative to craniotomy. MRgLITT was a more cost-effective treatment strategy than craniotomy in the management of patients with brain tumor radiation necrosis. The cost-effectiveness of MRgLITT may be attributed to a shorter LOS, lower complication odds, and higher home discharge odds in the immediate postoperative period and a lower risk of disease recurrence over the long-term follow-up.

Semaglutide for the secondary prevention of cardiovascular disease in people with overweight or obesity, but without diabetes: a cost-effectiveness analysis

Abstract Background The recently published trial, SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) [1], was the first study to demonstrate that the glucagon-like peptide 1 receptor agonist, semaglutide, was superior to placebo in reducing the risk of major cardiovascular events in people with existing cardiovascular disease (CVD) and a body mass index of ≥27kg/m² but without diabetes. Despite the promising clinical benefits, the high cost of the medication has raised concerns about its financial viability and accessibility within healthcare systems. Purpose To explore whether use of semaglutide in addition to standard care (background use of lipid lowering, anti-hypertensive and/or anti-platelet therapies) for the secondary prevention of CVD in people with overweight or obesity is cost effective from the Australian healthcare perspective. Methods A Markov model was developed based on the SELECT trial, to evaluate the clinical outcomes and costs of a hypothetical population treated with semaglutide versus placebo over 20 years. With each annual cycle, subjects were at risk of having non-fatal CVD events (MI or stroke) or dying. Treatment efficacy, transition probabilities, and utilities were derived from the SELECT trial and published literature. Costs were obtained from Australian sources. The cost of semaglutide at a dosage of 2.4 mg/week (in line with SELECT) was estimated to be ~A$80 per week or A$4175 per year. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. All outcomes and costs were discounted by 5% per year. Costs are reported in 2023 Australian dollars (A$). Results Over a 20 year time horizon, treatment of 1000 hypothetical subjects with overweight or obesity and existing CVD with semaglutide compared to placebo prevented 126 non-fatal CVD events and 81 deaths, and yielded an additional 0.46 discounted life years and 0.48 discounted QALYs per person. The difference in total discounted costs was A$43,955 per person. This equated to ICERs of A$99,853 per YoLS and A$96,055 per QALY gained. Conclusions Assuming a willingness-to-pay-threshold of A$50,000 per QALY gained, semaglutide would not be considered cost-effective for the secondary prevention of CVD in people with overweight or obesity in Australia at current prices. A price reduction of 52% to less than A$2000 per year would be required for it to be considered a cost-effective treatment strategy in this setting. Given the modest event rates reported in SELECT, cost-effectiveness is likely to improve if use of semaglutide is targeted to higher risk groups. Moreover, SELECT primarily focused on cardiovascular benefits, however data supporting the impact of semaglutide on a number of other weight-related complications are anticipated and will inform a more holistic understanding of its cost effectiveness.

Cost-Effectiveness of Hypoglossal Nerve Stimulation for Pediatric Severe Obstructive Sleep Apnea in Down Syndrome Patients.

To examine the cost-effectiveness of hypoglossal nerve stimulation (HGNS) implantation at an early age in simulated pediatric cohorts with Down Syndrome (DS) and severe obstructive sleep apnea (OSA). Cost-utility analysis. Hypothetical cohort. A Markov model simulated 3 pediatric cohorts with DS and OSA beginning at age 4 years until 21 years. Cohorts received HGNS implants in early childhood, late childhood, or adulthood at age 4, 13 (current FDA-approved age), or 18 years, respectively. Input model parameters were obtained from the literature and our institution. Outcomes were measured with an incremental cost-effectiveness ratio (ICER), measured in dollars per quality-adjusted life-year (QALY). Deterministic 1-way sensitivity analyses were conducted to evaluate the effects of parameter uncertainty. Results (total costs; total QALYs) across the time horizon were determined for each cohort: early implantation ($83,300.35; 15.79), late ($48,319.09; 14.98), and adult ($38,721.07; 14.55). ICERs were $48,892.47 per QALY for early vs late implantation, $43,471.15 per QALY for early vs adult implantation, and $30,959.58 per QALY for late vs adult implantation. All ICERs were below a willingness-to-pay threshold of $50,000 per QALY. Varying the discount rate and utility expectedly varied the ICERs and cost-effectiveness. Threshold analysis showed early implantation to be cost-effective for a HGNS implantation cost up to $62,230 compared to late implantation. The current study suggests HGNS is a cost-effective treatment strategy for pediatric patients with DS and severe OSA. Our findings also suggest cost-effectiveness at ages younger than 13, the current age of FDA approval.

Cemented Hemiarthroplasty Results in Substantial Cost Savings Over Uncemented Hemiarthroplasty for the Treatment of Femoral Neck Fractures in Patients Over 60 Years Old: A Markov Analysis

BackgroundWhile there is growing scientific evidence supporting superior outcomes following cemented versus uncemented hip hemiarthroplasty (HHA) in elderly femoral neck fractures (FNFs), the relative cost-effectiveness of this in the United States is unknown. Thus, the purpose of this study was to compare the cost-effectiveness of cemented versus uncemented HHA for the treatment of FNFs in patients > 60 years old in the United States, accounting for postoperative outcomes including periprosthetic fractures. MethodsA Markov model utilizing Monte Carlo microsimulation was developed to evaluate the outcomes and costs of patients at least 60 years of age (mean ± standard deviation, 84 ± 8 years) undergoing cemented versus uncemented HHA for the treatment of FNFs. Health utility values, transition probabilities, and upfront costs were derived from the published literature. Outcome measures included average total costs associated with each treatment (including those from patients who sustained a periprosthetic fracture), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). ResultsMean total costs resulting from cemented and uncemented HHA were $19,462 ± 3,581 and $21,997 ± 3,574, respectively (upfront costs from the published literature were $18,267 for cemented HHA and $16,803 for uncemented HHA). Average QALYs resulting from cemented and uncemented HHA were 4.0 ± 0.7 and 3.1 ± 0.6. The resulting ICER was -$2,688.9/QALY. Cemented HHA was found to be the most cost-effective treatment strategy in 89% of the patients in the Monte Carlo microsimulation model. ConclusionDespite documented higher upfront costs for cemented HHA, the averaged total costs over a 10-year time horizon were $2,534 less for cemented HHA than for uncemented HHA. In addition, cemented HHA resulted in an additional 0.9 QALYs relative to uncemented HHA. The findings of this United States-based study replicate the financial and quality-of-life benefits of cemented HHA for elderly FNFs seen in other health systems.

RpIFN-λ1 alleviates the clinical symptoms of porcine epidemic diarrhea

Porcine epidemic diarrhea (PED), caused by the porcine epidemic diarrhea virus (PEDV), primarily affects the jejunum and ileum of pigs. Interferons, glycoproteins with high species specificity and potent antiviral activity, are crucial in defending against viral infections. Unlike other interferons, interferon-lambda (IFN-λ) mainly acts on mucosal epithelial cells and exhibits robust antiviral activity at mucosal surfaces. However, the high cost limits the use of naturally extracted interferons in farming. In this study, we expressed recombinant porcine interferon-lambda 1 (rpIFN-λ1) in eukaryotic cells, demonstrating effective antiviral activity against PEDV in Vero E6 and IPI-FX cells. In vivo, rpIFN-λ1 alleviated clinical symptoms and intestinal damage, enhanced antioxidant capacity, reduced inflammation, and significantly improved the survival rate of piglets following PEDV infection. Both in vitro and in vivo studies confirmed that rpIFN-λ1 upregulated interferon-stimulated genes (ISGs) via the JAK-STAT pathway, thereby exerting antiviral effects. In conclusion, rpIFN-λ1 significantly inhibited PEDV replication and alleviated clinical symptoms. The selectivity of rpIFN-λ1 for intestinal cells and its ability to reduce viral shedding suggest that this agent is a promising antiviral for enteric viruses such as PEDV. Our findings highlight rpIFN-λ1 as a cost-effective, efficient, and novel strategy for antiviral treatment of PEDV.

Nutrition in the prevention and treatment of skeletal muscle ageing and sarcopenia: a single nutrient, a whole food and a whole diet approach.

Loss of skeletal muscle strength and mass (sarcopenia) is common in older adults and associated with an increased risk of disability, frailty and premature death. Finding cost-effective prevention and treatment strategies for sarcopenia for the growing ageing population is therefore of great public health interest. Although nutrition is considered an important factor in the aetiology of sarcopenia, its potential for sarcopenia prevention and/or treatment is still being evaluated. Nutrition research for sarcopenia utilises three main approaches to understand muscle-nutrition relationships, evaluating: single nutrients, whole foods and whole diet effects - both alone or combined with exercise. Applying these approaches, we summarise recent evidence from qualitative and quantitative syntheses of findings from observational and intervention studies of healthy older adults, and those with sarcopenia. We consider protein supplements, whole foods (fruits and vegetables) and the Mediterranean diet as exemplars. There is some evidence of beneficial effects of protein supplementation ≥ 0·8 g/kg body weight/d on muscle mass when combined with exercise training in intervention studies of healthy and sarcopenic older adults. In contrast, evidence for effects on muscle function (strength and physical performance) is inconclusive. There is reasonably consistent epidemiological evidence suggesting benefits of higher fruits and vegetables consumption for better physical performance. Similarly, higher adherence to the Mediterranean diet is associated with beneficial effects on muscle function in observational studies. However, intervention studies are lacking. This review discusses how current evidence may inform the development of preventive and intervention strategies for optimal muscle ageing and nutritional public policy aimed at combatting sarcopenia.

Evaluating cost-effectiveness of PFO management strategies: closure with Cardioform vs. Amplatzer, and treatment with medical therapy alone, for secondary stroke prevention

Aim The aim of this study was to evaluate the cost-effectiveness of patent foramen ovale (PFO) closure using CARDIOFORM Septal Occluders versus AMPLATZER Septal Occluders, as well as compared to Medical Therapy Alone, from a payor perspective in the United States. Methods An economic evaluation compared the value of CARDIOFORM, AMPLATZER, and Medical Therapy Alone. A Markov model simulated a cohort of 1,000 individuals with PFO and a history of cryptogenic stroke, with baseline demographic and clinical characteristics reflecting individuals enrolled in the REDUCE and RESPECT trials over a five-year time horizon. The costs and health consequences associated with complications and adverse events, including recurrent stroke, were compared over a time horizon of 5 years. Results PFO closure using CARDIOFORM was economically dominant, providing both cost-savings and improved effectiveness compared to closure with AMPLATZER. It resulted in an estimated savings of over $1.3 million, an additional 24.8 quality-adjusted life-years (QALYs) gained, and 28 strokes avoided in a cohort of 1,000 patients. When compared to Medical Therapy Alone, closure with CARDIOFORM was found to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of $36,697 per QALY gained. Sensitivity and scenario analysis showed the model findings to be highly robust across reasonable changes to baseline input values and assumptions. Conclusions The results of this analysis suggest that PFO closure using the CARDIOFORM Septal Occluder is the most cost-effective treatment strategy for patients with a PFO-associated stroke, particularly compared to AMPLATZER where it resulted in both cost-saving and improved patient outcomes.

The Impact of Body Composition on Mortality and Hospital Length of Stay after Endovascular and Open Aortic Aneurysm Repair: A Retrospective Cohort Study.

Background: Sarcopenia is an indicator of preoperative frailty and a patient-specific risk factor for poor prognosis in elderly surgical patients. Some studies have explored the prognostic significance of body composition parameters in relation to perioperative mortality after aortic repair and to mid- and long-term survival following endovascular aneurysm repair (EVAR). This study aimed to comprehensively investigate the effects of various body composition parameters, including but not limited to sarcopenia, on short- and long-term mortality as well as the length of hospital stay in two large cohorts of patients undergoing open surgical aortic repair (OSR) or EVAR. Methods: A single-institution retrospective cohort study included patients who underwent EVAR or OSR from January 2010 to December 2017. Several parameters of body composition on axial CT angiography images were analyzed, such as skeletal muscle area (SMA) with derived skeletal muscle index (SMI), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Results: 477 patients were included: 250 treated by OSR and 227 by EVAR; the mean age was 70.8 years (OSR) and 76.3 years (EVAR), with a mean follow-up of 54 months. Sarcopenia was associated with a prolonged length of hospital stay in EVAR patients but not in OSR patients (β coefficient 3.22; p-value 0.022 vs. β coefficient 0.391; p-value 0.696). Sarcopenia was an elevated one-year mortality risk post-EVAR compared to those without sarcopenia (p-value for the log-rank test 0.05). SMA and SMI were associated with long-term mortality in EVAR patients even after adjusting for multiple confounders (HR 0.98, p-value 0.003; HR 0.97, p-value 0.032). The analysis of the OSR cohort did not show a significant correlation between short- and long-term mortality and sarcopenia indicators. Conclusions: The results suggest that body composition could predict increased mortality and longer hospital stays in patients undergoing EVAR procedures. These findings were not confirmed in the cohort of patients who underwent OSR. Patients with sarcopenia and pre-operative malnutrition should be critically assessed to define the indication for treatment in this predominantly elderly and morbid cohort, despite EVAR procedures being less invasive. Body composition evaluation is an inexpensive and reproducible tool that can contribute to an improved decision-making process by identifying patients who will benefit most from EVAR, ensuring a more personalized and cost-effective treatment strategy. Further studies are planned to explore the added value of integrating body composition into a comprehensive risk stratification before aortic surgery.

Developing an 8-Week, Tele-Education Weight Control and Exercise Programme, and Evaluating Its Effects on Weight and Pain Reduction in Patients With Obesity and Knee Osteoarthritis: A Double-Blinded Randomised Clinical Trial.

Knee osteoarthritis (OA) is a leading cause of disability among the elderly and is often exacerbated by obesity. Research supports weight loss and exercise therapy as key strategies for managing knee OA-related disability. Concurrently, telemedicine is becoming a popular healthcare approach. This study aimed to develop and evaluate an 8-week tele-education programme's impact on weight control and knee OA outcomes. Participants with knee OA and obesity were included. Baseline data on pain (VAS index), physical activity (GPAQ questionnaire), and quality of life (EQ5D and KOOS questionnaires) were collected. Performance tests, including the 30-second Chair Stand test (30CST) and the Timed Up-and-Go test (TUG), were recorded. Participants were randomly divided into two groups: a control group receiving oral advice on diet and exercise, and an intervention group receiving educational videos on nutrition, lifestyle changes, physical activity, individualised exercises, and psychosocial support. Evaluations were repeated after 8weeks. Data from 25 of 30 participants were analysed. In the intervention group, body composition, waist, and abdominal circumference decreased significantly (p<0.05). The KOOS questionnaire showed significant improvements in pain, activity, and daily tasks (p=0.00). The EQ5D questionnaire and health satisfaction also showed positive results within the intervention group (p=0.00) and between groups (p=0.008). The pain index improved significantly within (p=0.00) and between groups (p=0.02). Functional test results were significant within the intervention group (p=0.00) and between groups (p=0.017 for 30CST and p=0.004 for TUG). An 8-week tele-education programme for weight control and exercise therapy in knee OA patients significantly improved body composition, quality of life, and functional performance. Given the costs of obesity and knee OA on both people and the health system, tele-education can be a cost-effective treatment strategy.

Real-world overall survival after alternative dosing for pembrolizumab in the treatment of non-small cell lung cancer: A nationwide retrospective cohort study with a non-inferiority primary objective

BackgroundHigh and increasing expenses on pembrolizumab ask for more cost-effective and sustainable treatment strategies to improve affordability of healthcare. Therefore, a part of the Dutch hospitals implemented an alternative, partially lower, weight-based dosing protocol for pembrolizumab. This provided the unique opportunity to compare the overall survival (OS) of the alternative pembrolizumab dosing protocol to standard dosing using a nationwide registry in non-small cell lung cancer (NSCLC) patients. MethodsThis is a retrospective cohort study with a non-inferiority primary objective. Forty hospitals in the Dutch Medication Audit and Dutch Lung Cancer Audit treated 1966 patients with NSCLC with first line pembrolizumab (mono- or combination therapy) between Jan 1st 2021, and Mar 31st, 2023. Alternative weight-based pembrolizumab dosing (100/150/200 mg Q3W or 200/300/400 mg Q6W) was administered to 604 patients, and 1362 patients received standard pembrolizumab dosing (200 mg Q3W or 400 mg Q6W). A Cox proportional hazard model with selected covariates was used to compare the OS between alternative and standard dosing protocols. The non-inferiority margin was set at a hazard ratio (HR) of 1.2 for OS. Non-inferiority is established by showing that the upper limit of the 95 % confidence interval (CI) of the HR of OS is smaller or equal to 1.2. ResultsDistribution of age (66.7 years +/-9.4), sex (45 % female) and treatment combinations were similar for both groups, comorbidity score was higher in the standard group. Median daily dose in the alternative dosing group was 22 % lower compared to the standard dosing group, 7.14 mg/day (interquartile range (IQR):5.48–8.04 mg/day) vs. 9.15 mg/day (IQR:8.33–9.52 mg/day), respectively. Alternative dosing was non-inferior to standard dosing regarding overall survival (adjusted HR 0.83, 95 %CI:0.69–1.003). ConclusionThis large, retrospective real-world analysis supports the hypothesis that the alternative, partially lower pembrolizumab dosing protocol in NSCLC maintains treatment effectiveness while reducing treatment costs.

Osteochondroplasty with or without labral repair is more cost-effective than arthroscopic lavage with or without labral repair for treatment of young adults with femoroacetabular impingement: A cost-utility analysis based on data from a randomized controlled trial

ObjectivesThe objective of this study was to conduct a cost–utility analysis of osteochondroplasty with or without labral repair compared to arthroscopic lavage with or without labral repair for femoroacetabular impingement (FAI) from a Canadian public payer perspective. MethodsA Markov model was constructed to compare the lifetime quality-adjusted life years (QALYs) and costs of the two treatment strategies. The target population was surgical FAI patients aged 36 years. The primary data source was patient-level data from the Femoroacetabular Impingement Randomised Controlled Trial, which evaluated the efficacy of the surgical correction of FAI via arthroscopic osteochondroplasty with or without labral repair compared to arthroscopic lavage with or without labral repair in Canada. Long-term data were extrapolated using a generalized gamma model. The primary outcome was the incremental cost-effectiveness ratio, calculated by dividing the difference in costs by the difference in QALYs between osteochondroplasty and lavage, with or without labral repair. Probabilistic sensitivity analyses and one-way sensitivity analyses were used to characterize uncertainty of model parameters and assumptions. ResultsOver a lifetime horizon, osteochondroplasty, with or without labral repair, had a greater expected benefit (0.63 QALYs gained per patient) and lower costs ($955.89 saved per patient), as compared with lavage with or without labral repair. Probabilistic sensitivity analyses demonstrated that the probability of osteochondroplasty, with or without labral repair, being cost-effective was 90.5% at a commonly used willingness-to-pay threshold of $50,000/QALY in Canada. Across all one-way sensitivity analyses, osteochondroplasty with or without labral repair remained a cost-effective option. ConclusionOver a lifetime time horizon, osteochondroplasty, with or without labral repair, is a cost-effective treatment strategy for young adults with FAI. Future research involving real-word data is needed to further validate these findings. Level of evidenceIII.

Impact of new antifungal medications on onychomycosis prescriptions and costs in Japan: A nationwide claims database study.

Onychomycosis, a fungal nail infection, is a common dermatological condition in Japan, with a prevalence of approximately 5%-10%. Despite the introduction of new antifungal medications and updated treatment guidelines published in 2019, data on real-world prescription trends and the associated medical costs are limited. This study aimed to investigate the prescription patterns and medical costs of topical and oral antifungal medications for onychomycosis in Japan from fiscal years 2014 to 2021 using the National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data. We analyzed the annual prescription volumes and medical costs of four antifungal medications: efinaconazole, luliconazole, fosravuconazole, and terbinafine. The prescription volume of efinaconazole, a topical medication launched in 2014, rapidly increased and dominated the market share. Fosravuconazole, an oral medication introduced in 2018, showed an increasing trend, coinciding with a decline in efinaconazole prescriptions. Terbinafine, a well-established oral medication, experienced a substantial decrease in prescription volume. The sex- and age-adjusted prescription volume per 100 000 population was higher among older adults, particularly for efinaconazole. The total medical costs for onychomycosis treatment more than doubled in fiscal year 2015 compared with that for 2014, mainly driven by efinaconazole prescriptions, and exceeded 30 billion Japanese yen in fiscal years 2019-2021. The costs slightly decreased in fiscal years 2020 and 2021, possibly due to the introduction of fosravuconazole. The predominance of topical prescriptions, especially in older adults, raises concerns regarding adherence to the Japanese guidelines that recommend oral antifungals as the first-line treatment for onychomycosis. The substantial increase in medical costs also highlights the economic burden of onychomycosis and the need for cost-effective treatment strategies. This study provides valuable insights into the real-world prescription trends and medical costs of onychomycosis treatment in Japan, suggesting an opportunity to assess potential gaps between guideline recommendations and clinical practice.

Health and Economic Outcomes of Pembrolizumab in the Treatment of Metastatic Non-small Cell Lung Cancer (mNSCLC) and Melanoma in Italy.

In Italy, the management of metastatic non-small cell lung cancer and melanoma leads to significant healthcare challenges, necessitating cost-effective treatment strategies and offering valuable insights for healthcare policymakers and stakeholders. This study was designed to assess the costs, quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs) associated with the health and economic outcomes of (1) pembrolizumab-combined chemotherapy administered as a first-line treatment for metastatic non-squamous and squamous non-small cell lung cancer (NSCLC) where the tumour presents with a programmed death-ligand 1 expression level <50% and of (2) adjuvant pembrolizumab treatment for stage III melanoma. Three cost-effectiveness models developed by MSD were investigated for each treatment indication. A unique model was built to assess the overall effect of pembrolizumab versus chemotherapy or watchful waiting in patients with lung cancer or melanoma, respectively. Theoretical cohorts of patients with metastatic squamous and non-squamous NSCLC were followed over time using a partitioned survival model with weekly cycles. A weekly cycle Markov model was employed for melanoma. The analysis was conducted from the Italian National Health Service perspective, considering a time horizon of 40 years (lifetime). A single closed cohort of treatable patients was followed over time for each indication (4000, 7000 and 900 for NSCLC squamous, non-squamous and melanoma, respectively). The costs evaluated included those for adverse drug events, non-drug disease management, subsequent treatment and terminal care. Drug acquisition and administration costs were excluded. For each treatment indication assessed, pembrolizumab produced downstream direct cost offsets (- €122,498,568, -€133,369,076 and -€32,993,242 for NSCLC squamous, non-squamous and melanoma indications, respectively), increased quality of life (+2088, +5317 and +2307 QALYs for NSCLC squamous, non-squamous and melanoma indications, respectively) and reduced disability (-2658, -7202 and -3029 DALYs for NSCLC squamous, non-squamous and melanoma indications, respectively). Across indications, the total cost offsets of pembrolizumab were -€288,860,885, with 9712 QALYs gained and 12,889 DALYs avoided. The analysis demonstrated that, compared with chemotherapy, pembrolizumab is more cost effective in Italy as a first-line treatment in patients with metastatic squamous or non-squamous NSCLC and, if compared with watchful waiting, as adjuvant treatment in patients with stage III melanoma. The present analysis suggested that pembrolizumab use could lead to important health benefits for patients while offsetting a portion of cancer care costs.

Origins of High Air Sensitivity and Treatment Strategies in O3-Type NaMn1/3 Fe1/3Ni1/3O2.

Sodium-ion layered oxides are one of the most highly regarded sodium-ion cathode materials and are expected to be used in electric vehicles and large-scale grid-level energy storage systems. However, highly air-sensitive issues limit sodium-ion layered oxide cathode materials to maximize cost advantages. Industrial and scientific researchers have been developing cost-effective air sensitivity treatment strategies with little success because the impurity formation mechanism is still unclear. Using density functional theory calculations and ab initio molecular dynamics simulations, this work shows that the poor air stability of O3-type NaMn1/3Fe1/3Ni1/3O2 (NMFNO) may be as follows: (1) low percentage of nonreactive (003) surface; (2) strong surface adsorption capacity and high surface reactivity; and (3) instability of the surface sodium ions. Our physical images point out that the high reactivity of the NMFNO surface originates from the increase in electron loss and unpaired electrons (magnetic moments) of the surface oxygen active site as well as the enhanced metal coactivation effect due to the large radius of the sodium ion. We also found that the hydrolysis reaction requires a higher reactivity of the surface oxygen active site, while the carbon hybridization mode transformation in carbonate formation depends mainly on metal activation and does not even require the involvement of surface oxygen active sites. Based on the calculation results and our proposed physical images, we discuss the feasibility of these treatment strategies (including surface morphology modulation, cation/anion substitution, and surface configuration design) for air-sensitive issues.

New insight into enhanced carbon recovery from anaerobic fermentation of waste activated sludge with cation exchange resin coupled with NaCl pretreatment

Carbon recovery from waste activated sludge has been attracting considerable attention. However, the migration and transformation patterns of carbon sources between the phases have rarely been reported. In this study, a novel strategy using cation exchange resin (CER) coupled with sodium chloride (NaCl) to enhance carbon recovery through anaerobic fermentation (AF) was proposed. The results demonstrated that CER coupled with NaCl destroyed OH and CO stretching in amide I while promoting the formation of β-sheet and random coil structures, leading to sludge disintegration. This significantly improved the kinetics of endogenous carbon release, resulting in the release of 1146.33 mg/L of carbon from the solid sludge into the liquid phase. Approximately 75.61 % of the initial carbon source was bio-transformed into short-chain fatty acids. Correspondingly, carbon recovery was significantly increased up to 852.23 mg C/L, 4.57 times that of the control. Mechanism exploration revealed that carbon source recovery was significantly elevated by the synergistic effect of CER and NaCl. CER effectively removed high-valence cations from extracellular polymeric substance (EPS), weakening its bridging and adsorption-electro neutralization capabilities, promoting protein deflocculation, and triggering EPS disruption to release extracellular carbon sources. NaCl disrupted the ionic strength and distribution inside and outside microbial cells, creating an osmotic pressure difference that resulted in cell plasmolysis and lysis, ultimately inducing the release of intracellular carbon sources. Economic and carbon emission reduction benefit analyses verified that the CER coupled with NaCl pretreatment is a cost-effective sludge treatment strategy. This study illustrates the carbon source migration and transformation pathways in the CER coupled with NaCl-assisted AF process, providing guidance for sustainable sludge management.

Early Surgery for Partial Tears of the Ulnar Collateral Ligament May Be More Cost-Effective and Result in Longer Playing Careers Than Nonoperative Management for High-Level Baseball Pitchers: A Decision-Analytic Markov Model–Based Analysis

Background: Nonoperative management versus early reconstruction for partial tears of the medial ulnar collateral ligament (MUCL) remains controversial, with the most common treatment options for partial tears consisting of rest, rehabilitation, platelet-rich plasma (PRP), and/or surgical intervention. However, whether the improved outcomes reported for treatments such as MUCL reconstruction (UCLR) or nonoperative management with a series of PRP injections justifies their increased upfront costs remains unknown. Purpose: To compare the cost-effectiveness of an initial trial of physical therapy alone, an initial trial of physical therapy plus a series of PRP injections, and early UCLR to determine the preferred cost-effective treatment strategy for young, high-level baseball pitchers with partial tears of the MUCL and with aspirations to continue play at the next level (ie, collegiate and/or professional). Study Design: Economic and decision analysis; Level of evidence, 2. Methods: A Markov chain Monte Carlo probabilistic model was developed to evaluate the outcomes and costs of 1000 young, high-level, simulated pitchers undergoing nonoperative management with and without PRP versus early UCLR for partial MUCL tears. Utility values, return to play rates, and transition probabilities were derived from the published literature. Costs were determined based on the typical patient undergoing each treatment strategy at the authors’ institution. Outcome measures included costs, acquired playing years (PYs), and the incremental cost-effectiveness ratio (ICER). Results: The mean total costs resulting from nonoperative management without PRP, nonoperative management with PRP, and early UCLR were $22,520, $24,800, and $43,992, respectively. On average, early UCLR produced an additional 4.0 PYs over the 10-year time horizon relative to nonoperative management, resulting in an ICER of $5395/PY, which falls well below the $50,000 willingness-to-pay threshold. Overall, early UCLR was determined to be the preferred cost-effective strategy in 77.5% of pitchers included in the microsimulation model, with nonoperative management with PRP determined to be the preferred strategy in 15% of pitchers and nonoperative management alone in 7.5% of pitchers. Conclusion: Despite increased upfront costs, UCLR is a more cost-effective treatment option for partial tears of the MUCL than an initial trial of nonoperative management for most high-level baseball pitchers.

Cost-Effectiveness and Budget Impact Analyses of Selective Internal Radiation Therapy versus Atezolizumab Plus Bevacizumab from a German Statutory Health Insurance Perspective.

To compare personalized dosimetry with yttrium-90 (90Y)-loaded glass microspheres (SIRT) vs atezolizumab and bevacizumab (A+B) in hepatocellular carcinoma (HCC) treatment in terms of cost-effectiveness and budget impact from a German statutory health insurance (SHI) perspective. Cost-effectiveness analysis (CEA) and budget impact analysis (BIA) models were developed in MS Excel. The available key studies (IMbrave150 and DOSISPHERE-01) suggest that both strategies are comparable in terms of progression-free survival and overall survival in HCC, but a difference in severe adverse events (SAE) in favor of SIRT was observed. Accordingly, the CEA model investigates the endpoints "cost per SAE avoided" and "cost per quality-adjusted life year (QALY) gained", whereas the BIA simulates the impact of a stepwise re-allocation of current market share to the option which emerges as more cost-effective from the CEA. The model suite estimated a mean annual total per-patient costs of € 29,984 for SIRT, compared to € 75,725 for A+B. SIRT was associated with a lower number of SAE and a higher number of QALYs compared to A+B. Switching additionally 25% of the eligible patients (≈500) from systemic therapy to SIRT could generate annual savings of approximately € 22.6 million Euros to the SHI. SIRT was identified as dominant treatment strategy. SIRT use not only saves SHI expenditure compared to systemic immunotherapy but also yields extra QALYs. This positions SIRT as the dominant and more cost-effective treatment strategy for patients with HCC. The savings to the SHI system, derived from the BIA conducted, become increasingly significant with rising adoption rates of SIRT.

An Evaluation of the Health Economics of Postnatal Depression Prevention and Treatment Strategies in China: A Cost-Effectiveness Analysis.

The primary objectives of this study are to assess the cost-effectiveness of early postnatal screening and prenatal psychological interventions for the prevention and treatment of postpartum depression (PPD) among Chinese pregnant women. Additionally, we aim to explore the most cost-effective prevention and treatment strategies for PPD in China. We used TreeAge 2019 to construct a decision tree model, with the model assuming a simulated queue size of 10,000 people. The model employed Monte Carlo simulation to assess the cost-effectiveness of PPD prevention and treatment strategies. Transfer probabilities were derived from published studies and meta-analyses. Cost and effectiveness data were obtained from published sources and relevant studies. Incremental cost-effectiveness ratios (ICERs) were used to describe the results, with willingness-to-pay (WTP) thresholds set at China's gross domestic product (GDP) per capita. Compared to the usual care group, the cost per additional quality-adjusted life year (QALY) for the early postnatal screening group and the prenatal psychological interventions is USD 6840.28 and USD 3720.74, respectively. The cure rate of mixed treatments for PPD has the greatest impact on the model, while patient participation in treatment has a minor impact on the cost-effectiveness of prevention and treatment strategies. Both early postnatal screening and prenatal psychological interventions are found to be highly cost-effective strategies for preventing and treating PPD in China. Prenatal psychological interventions for pregnant women are the most cost-effective prevention and treatment strategy. As such, from the perspective of national payers, we recommend that maternal screening for PPD be implemented in China to identify high-risk groups early on and to facilitate effective intervention.

Environmental enrichment alleviates hyperalgesia by modulating central sensitization in a nitroglycerin-induced chronic migraine model of mice

BackgroundChronic migraine (CM) is a debilitating neurofunctional disorder primarily affecting females, characterized by central sensitization. Central sensitization refers to the enhanced response to sensory stimulation, which involves changes in neuronal excitability, synaptic plasticity, and neurotransmitter release. Environmental enrichment (EE) can increase the movement, exploration, socialization and other behaviors of mice. EE has shown promising effects in various neurological disorders, but its impact on CM and the underlying mechanism remains poorly understood. Therefore, the purpose of this study was to determine whether EE has the potential to serve as a cost-effective intervention strategy for CM.MethodsA mouse CM model was successfully established by repeated administration of nitroglycerin (NTG). We selected adult female mice around 8 weeks old, exposed them to EE for 2 months, and then induced the CM model. Nociceptive threshold tests were measured using Von Frey filaments and a hot plate. The expression of c-Fos, calcitonin gene-related peptide (CGRP) and inflammatory response were measured using WB and immunofluorescence to evaluate central sensitization. RNA sequencing was used to find differentially expressed genes and signaling pathways. Finally, the expression of the target differential gene was investigated.ResultsRepeated administration of NTG can induce hyperalgesia in female mice and increase the expression of c-Fos and CGRP in the trigeminal nucleus caudalis (TNC). Early exposure of mice to EE reduced NTG-induced hyperalgesia in CM mice. WB and immunofluorescence revealed that EE inhibited the overexpression of c-Fos and CGRP in the TNC of CM mice and alleviated the inflammatory response of microglia activation. RNA sequencing analysis identified that several central sensitization-related signaling pathways were altered by EE. VGluT1, a key gene involved in behavior, internal stimulus response, and ion channel activity, was found to be downregulated in mice exposed to EE.ConclusionEE can significantly ameliorate hyperalgesia in the NTG-induced CM model. The mechanisms may be to modulate central sensitization by reducing the expression of CGRP, attenuating the inflammatory response, and downregulating the expression of VGluT1, etc., suggesting that EE can serve as an effective preventive strategy for CM.