Journal of Medical Economics

COVID-19 remains a substantial public health challenge in the Netherlands. Next-generation COVID-19 vaccine, mRNA-1283, is approved in the European Union, with potential for higher relative vaccine efficacy compared with originally-licensed COVID-19 vaccines. Its potential public health and economic impact, in adults [≥]60 years and high-risk 18-59 years, was modelled versus no vaccination and originally-licensed mRNA-1273 and BNT162b2, adapting a published static Markov model with 1-year time horizon. COVID-19 burden reflected two full post-pandemic seasons. Vaccine efficacy versus mRNA-1273 was based on pivotal phase 3 NextCOVE trial data; efficacy versus BNT162b2 was derived from an indirect treatment comparison. The economically justifiable price (EJP) of mRNA-1283 versus no vaccination, and price premiums over existing vaccines, were determined at a willingness-to-pay threshold of {euro}50,000/quality-adjusted life-year (QALY) gained. Without COVID-19 vaccination, an estimated 460,000 infections, 23,800 hospitalizations and 5,300 deaths would occur. With current coverage, mRNA-1283 was estimated to prevent 68,000 infections, 5,400 hospitalizations, and 1,200 deaths, saving 9,667 QALYs and over {euro}66.5 million in treatment costs. The EJP was {euro}238 versus no vaccination. Compared with mRNA-1273 and BNT162b2, mRNA-1283 was estimated to prevent additional burden (e.g., 1,309 and 1,679 hospitalizations, respectively), and was cost-effective at an incremental EJP of {euro}62 versus mRNA-1273, and {euro}80 versus BNT162b2. The results support continued COVID-19 vaccination to mitigate the ongoing health and societal burden of SARS-CoV-2 in the Netherlands. The comparative analyses indicate that mRNA-1283 may be associated with substantial health benefits over originally-licensed mRNA vaccines; consequently, its use may further improve health outcomes and economic efficiency within COVID-19 vaccination programs.

BackgroundThe United Nations General Assembly High-level Meeting on Antimicrobial Resistance (UNGA HLM-AMR) committed to a target that 70% of global human antibiotic use (ABU) should be from the Access group of the WHO AWaRe system. MethodsWe used 2019 IQVIA MIDAS(R) global ABU Quarterly value sales, volumes (kg/SU) and average ex-manufacturer prices to evaluate price per daily defined dose (DDD) by AWaRe group across countries. IQVIA MIDAS volumes/value data reflect public, private, or mixed sectors. We estimated potential national pharmaceutical expenditure savings if i) the UNGA 70% Access target was met, and ii) national ABU aligned with the WHO Model List of Essential Medicines (EML). We evaluated 7-day treatment prices for common oral and parenteral antibiotics across AWaRe groups. We measured affordability in middle-income countries (MICs) by income group, as the percentage of the population at risk of falling below national poverty lines if paying out-of-pocket, using income distributions and generalised beta distributions of the second kind. Prices were reported in 2019 international dollars (I$). ResultsVolume-weighted ex-manufacturer prices per DDD were lower for Access (I$1{middle dot}2, IQR I$0{middle dot}7) than Watch (I$2{middle dot}6, IQR I$2{middle dot}1) and highest (I$83{middle dot}8, IQR I$80{middle dot}9) for Reserve antibiotics. Lower prices were seen in high-income countries for Access antibiotics. Meeting the 70% Access target could save countries I$0{middle dot}1 million-I$4{middle dot}9 billion annually. Global savings could reach I$10{middle dot}4 billion if only WHO EML-listed antibiotics were used. Seven-day parenteral meropenem could put 7% (IQR 9%) of the population in MICs at risk of impoverishment. ConclusionAntibiotic policies focused on achieving the UNGA-AMR 70% Access target could generate significant potential national and global expenditure savings. FundingThis work was supported by the Wellcome Trust (304681/Z/23/Z) as part of the Antibiotic Data to Inform Local Action (ADILA) project and the Global Antibiotic Policy initiative (GAPi) project (RES 2024-495).

Background Catch-up vaccination will be pivotal for achieving WHOs cervical cancer elimination goals in low- and middle-income countries (LMICs). We assessed the health-economic impact of catch-up HPV vaccination for females in LMICs. Methods Using IARCs METHIS modelling platform and data from 132 LMICs, we simulated HPV catch-up vaccination beyond the primary target age, varying the maximum age up to 30 years. Budget impact was expressed as a share of national five-year immunization budgets and current health expenditure. We conducted cost-effectiveness analyses for a smaller subset of countries for which high-quality cervical cancer treatment costs were available. Findings Catch-up HPV vaccination up to age 30 in LMICs could prevent 9.2 million cervical cancer cases over the lifetime among females aged 9-30 years. Across countries, budget impact ranged from 0.007%-2.24% of five-year health expenditure and 0.002%-236.65% of immunization budgets, with vaccine procurement comprising about 70% of costs. Gavi support could reduce costs by nearly 70% for catch-up up to age 18. Catch-up vaccination up to age 30 was cost-effective in almost all evaluated countries, except in one where cost-effectiveness was achieved up to age 21. Interpretation In LMICs, after achieving adequate coverage in the primary target group (9-14 years), expanding HPV catch-up vaccination would be impactful and cost-effective. Sustainable financing, Gavi support, and cost-minimization strategies are crucial for successful catch-up programmes and progress toward cervical cancer elimination.

BackgroundThe Most Favored Nation (MFN) policy is a mechanism that incorporates foreign prices to determine the maximum allowable net price for any branded drug within US government-funded healthcare. Two proposed rules, the Global Benchmark for Efficient Drug Pricing ("GLOBE") (90 Fed. Reg. 60,244) for Medicare Part B and the Guarding US Medicare Against Rising Drug Costs ("GUARD") (90 Fed. Reg. 60,338) for Medicare Part D, invoke the Center for Medicare and Medicaid Innovation Centers payment and service model demonstration and waiver authority, under Section 1115A of the Social Security Act (42 U.S.C. [§] 1315a), to calculate the US MFN price which is the lowest average price within a basket of specified foreign countries. Unlike voluntary manufacturer agreements, GLOBE and GUARD would mandate participation from all applicable manufacturers. MethodsWe derive MFNs potential impact on Medicare pricing from a proprietary dataset provided by IQVIA which contained net prices for the top 37 oncology products by total US sales from January 1, 2019 through June 30, 2025 ranked by total US sales in the following countries: Australia, Belgium, France, Germany, Ireland, Italy, South Africa, Spain, Switzerland, the UK, and the US. For each drug, we select the lowest GDP-adjusted international price from a basket of those countries within 60% of the US GDP per capita, adjusted for purchasing power parity, and calculate the reduction in US price required to match its MFN price, and hence the corresponding reduction in revenues under MFN. A retrospective Net Present Value (NPV) analysis is then used to address the counterfactual question of whether each drug would have been developed had MFN pricing been in place at the time of its FDA approval. ResultsUnder MFN, the average reduction in US prices across our drug cohort was 67%. Eighty-four percent of the 37 cancer drugs in our cohort evidenced a negative NPV if MFN had been in place at the time of their FDA approval and the commercial market is impacted. When the analysis is restricted to MFNs impact on Medicare, the indications for these lost drugs have a total US population of 2.4 million patients. When the analysis is combined across the Medicare and commercial markets, the loss of lead indications impacts over 15 million US patients. ConclusionsMandatory MFN policies reduce the financial incentives required to develop cancer medicines; our projections show a substantial decline in new cancer drug launches and will likely lead companies to pursue indications for populations outside Medicares authority. If so, MFN will reduce the number of new therapies for the very population the Executive Orders are allegedly designed to aid: the Medicare-aged population who require effective new therapies in areas of high unmet medical need, such as late-stage cancers. This creates the perverse outcome of a policy nominally designed to help Medicare beneficiaries by instead redirecting innovation away from their most urgent therapeutic needs.

ObjectivesDigital biomarkers offer scalable screening for type 2 diabetes, yet adoption is stalled by uncertainty regarding economic viability. This study evaluates the cost-effectiveness and budget impact of digital screening compared to opportunistic screening from a Swiss payer perspective. MethodsA probabilistic Markov cohort model was developed to simulate at-risk Swiss adults (age [≥]45, BMI [≥]25 kg/m{superscript 2}) over a 40-year horizon. The model incorporates a digital attrition parameter, inputs derived from Swiss-specific sources (e.g., the CoLaus study and FSO life tables), and statutory tariffs. Costs and outcomes were discounted at 3.0%. ResultsIn the deterministic base-case, digital screening yielded an incremental cost-effectiveness ratio of CHF 2,912 per quality-adjusted life-year gained. Probabilistic sensitivity analysis indicated a 93.2% probability of cost-effectiveness at the CHF 50,000 threshold. The budget impact analysis estimated a Year 1 gross investment budget of CHF 27 million to identify prevalent cases, followed by long-term savings from averted complications. ConclusionsDigital screening can be highly cost-effective in Switzerland. While the required Year 1 gross investment poses a liquidity challenge, reimbursement via pathway-oriented models under the Swiss tariff could align incentives with long-term complication avoidance.

BackgroundHigh-dose inactivated influenza vaccination (HD-IIV) demonstrates superior effectiveness versus standard-dose vaccination (SD-IIV) in adults aged [≥]60 years. A recent meta-analysis integrated complementary evidence sources of representing over 85 million individuals across 14 influenza seasons. MethodsA previously developed model was updated using life-time horizon and societal perspective. Updated parameters included demographics, costs, hospitalization rates, and relative vaccine effectiveness (rVE): RCT evidence (24% for ILI, 7% for cardiorespiratory hospitalizations) and RCT + real-world evidence (RWE) (15% for ILI, 8% for cardiorespiratory hospitalizations). ResultsHD-IIV resulted in incremental cost-effectiveness ratios of {euro}7,300/QALY (RCT evidence) and {euro}5,800/QALY (RCT+RWE evidence). Implementation would prevent 7,200 general practitioner visits, 6,300 cardiorespiratory hospitalizations, and 269 deaths, by using RCT evidence. Probabilistic sensitivity analysis demonstrated >99% probability of cost-effectiveness at {euro}20,000/QALY threshold for both RCT and RCT+RWE evidence. ConclusionsHD-IIV remains highly cost-effective for Dutch adults aged [≥]60 years under updated evidence scenarios, supporting implementation in the national immunization programme. HighlightsO_LIThe economic analysis of high-dose inactivated influenza vaccine was updated. C_LIO_LIRelative vaccine effectiveness of HD-IIV incorporating recent evidence was used. C_LIO_LIHD-IIV remains cost-effective in Dutch adults aged [≥]60. C_LI

BackgroundQuadruple therapy, comprising an angiotensin receptor-neprilysin inhibitor (ARNI), {beta}-blocker, mineralocorticoid receptor antagonist (MRA), and sodium-glucose cotransporter 2 inhibitor (SGLT2i), is guideline-recommended for heart failure with reduced ejection fraction (HFrEF). However, uptake in Singapore remains low. This study evaluated the cost-effectiveness of scaling up quadruple therapy from the current 30% uptake to realistic (80%) and stretch (100%) targets. MethodsWe developed a decision-analytic model combining a decision tree and Markov structure to simulate clinical and economic outcomes over a 10-year horizon from the Singapore healthcare system perspective. Transition probabilities were estimated using local real-world data for current regimens, and published literature for quadruple therapy. Costs were derived from hospital billing data and drug utilisation patterns. A probabilistic sensitivity analysis (1,000 simulations) assessed uncertainty. The willingness-to-pay (WTP) threshold was S$45,000 per quality-adjusted life year (QALY) gained. ResultsBoth scale-up scenarios were cost-effective. Compared to current practice, the 80% uptake scenario resulted in an incremental cost of S$2.57M and 110 additional QALYs (ICER: S$23,392/QALY) for 1000 patients over 10 years, while the 100% uptake scenario yielded 137 QALYs at an incremental cost of S$2.88M (ICER: S$21,117/QALY). Under conservative assumptions, both scenarios remained cost-effective. The probability of being cost-effective was 92% (80% uptake) and 96% (100% uptake). InterpretationScaling up quadruple therapy for HFrEF in Singapore is highly cost-effective. Implementation strategies to close the treatment gap should be prioritised to improve outcomes and maximise value in heart failure care.

Purpose: Neurogenic dysphagia is prevalent in neurological inpatients and associated with adverse outcomes, yet its independent economic impact after adjustment for frailty and functional status remains poorly quantified. We aimed to estimate the independent effect of dysphagia on hospital length of stay (LOS) and costs, to test whether this effect differs between geriatric and non-geriatric patients, and to quantify the probability and magnitude of cost savings from improvements in swallowing function. Methods: We analysed 10,375 neurological inpatient cases (2021-2024) at a German university hospital. Dysphagia was defined by fiberoptic endoscopic evaluation of swallowing (FEES) or ICD-10 R13 coding (n = 1,382; 13.3%). Bayesian Gamma-log regression with informative priors from historical data and published literature was used to model LOS and total case costs (German DRG), adjusted for age, sex, Hospital Frailty Risk Score (HFRS, R13-adjusted), self-care index ("Selbstpflege-Index", SPI), stroke status, and emergency admission. A geriatric cohort was defined as age >=70 and adjusted HFRS >=5 (n = 2,053; 19.8%). Posterior predictive simulation estimated cost savings for hypothetical improvements of 1-3 points on the Functional Oral Intake Scale (FOIS). Results: After comprehensive adjustment, dysphagia was independently associated with 46.5% longer LOS (posterior ratio 1.465; 95% credible interval [CrI] 1.397-1.537) and 28.2% higher total case costs (ratio 1.282; CrI 1.213-1.354). The dysphagia x geriatric interaction was small but credible and ran in opposite directions: slightly attenuated for LOS (interaction ratio 0.908, CrI 0.837-0.986) but slightly amplified for costs (1.096, CrI 1.012-1.185), consistent with complexity-driven DRG grouping in geriatric patients. The absolute economic burden remained larger in the geriatric cohort due to higher baseline costs. In the geriatric cohort, a one-point FOIS improvement yielded a 74.3% posterior probability of LOS-based savings (mean EUR 555/case); at three points, this rose to 84.2% (mean EUR 1,115/case). The direct cost model confirmed high benefit probabilities from the payer's perspective (82.6% at dFOIS = 3). Conclusions: Neurogenic dysphagia is an independent and substantial driver of hospital LOS and costs in neurological inpatients, even after adjustment for frailty and functional status. The proportional effect on costs is slightly larger in geriatric patients, while the LOS effect is slightly smaller, consistent with the mechanics of the G-DRG system. Bayesian simulation indicates that improvements in swallowing function carry a high probability of generating cost savings, supporting the characterisation of dysphagia as a modifiable economic target with particular relevance to geriatric neurology.

BackgroundOlder adults face a disproportionately high risk of severe influenza, yet the standard inactivated vaccine (IIV) offers suboptimal protection in this population. This study evaluates the cost-effectiveness of replacing IIV with the recombinant influenza vaccine (RIV) for adults aged [≥]50, [≥]65, and [≥]80 years in Hong Kong. MethodsA decision tree model was used to compare RIV with IIV for adults aged [≥]50, [≥]65, and [≥]80 years in Hong Kong, from a societal perspective. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were evaluated with the impact of parameter uncertainty on the results assessed via deterministic and probabilistic sensitivity analyses. ResultsFor adults [≥]50 years, RIV increased total costs by USD5.1 (HKD39.8) per person and gained 0.00012 QALYs (ICER: USD40,659 [HKD317,140] per QALY) compared to IIV. Among adults [≥]65 years, RIV cost USD6.0 (HKD46.8) more and gained 0.00021 QALYs (ICER: USD29,077 [HKD226,801] per QALY). For adults [≥]80 years, RIV cost USD3.2 (HKD25.0) more and gained 0.00015 QALYs (ICER: USD21,092 [HKD164,518] per QALY). ICERs were less than willingness-to-pay thresholds of one to three times Hong Kongs gross domestic product per capita. ConclusionsRIV is cost-effective compared with IIV for adults [≥]50, [≥]65, and [≥]80 years in Hong Kong, with the lowest ICER observed in individuals [≥]80 years.

BackgroundUterine fibroids cause significant morbidity, psychosocial stress, and poor quality of life due to symptoms including heavy menstrual bleeding, anemia, pain, and bulk symptoms, as well as reproductive complications including infertility, early pregnancy loss, and preterm birth. Fibroids represent a 42.2 billion USD annual economic burden to the United States healthcare system. Despite reported delays in diagnosis of fibroids even in symptomatic women, clinical guidelines do not recommend screening for fibroids. High risk patient groups are well known. Earlier detection of fibroids through ultrasound screening could allow for earlier intervention with secondary prevention strategies or less invasive treatment options and improve the quality of life of women living with fibroids. ObjectiveThe study aimed to evaluate the cost-effectiveness of annual ultrasound screening for fibroids in women aged 25-54 years in the United States. Study DesignIn this economic evaluation, conducted in January-February 2026, a decision-analytic Markov model was developed using a healthcare payer perspective to analyze the cost-effectiveness of ultrasound screening for women in the United States. The time horizon was 25 to 55 years of age. Costs were adjusted for inflation to 2025 average according to the yearly medical care index of the United States consumer price index. Discounting (3% per cycle) and half-cycle corrections were calculated. Deterministic and probabilistic sensitivity analyses were performed to explore uncertainty, analyzed using TreeAge Pro Healthcare software. Model variables were obtained from published literature. All women residing in the United States aged 25-54 years were assumed to have been invited to the screening program. ResultsUltrasound screening for fibroids for women was found to be not only cost-effective but also cost-saving, with an incremental cost-effectiveness ratio (ICER) of -$56,605.631 per QALY (quality-adjusted life-year) gained in the base-case analysis, at a willingness to pay threshold of $30,000 per QALY. Ultrasound screening was cost-effective at all starting ages from 25 to 54 years, with even greater benefit at younger ages. Sensitivity analyses demonstrated the robustness of these findings across a wide range of variable ranges. Ultrasound screening for fibroids showed a cumulative potential to save $1,169 billion and increase 20.7 million QALYs per year compared to no screening for a population of 63.89 million American women between 25 and 54 years old. The subset of 9.32 million Black American women experienced greater benefits, with potential savings of 183 billion and an increase of 3 million QALYs. ConclusionBased on the model-based analysis, annual ultrasound screening for uterine fibroids for women aged 25-54 years in the United States was cost-effective and cost-saving, even more so for Black women. These model-based findings highlighted the potential value of guidelines for annual ultrasound screening for fibroids, which could enable earlier diagnosis, secondary prevention, and timely intervention, with positive impact on both quality of life and healthcare costs. Tweetable StatementAnnual ultrasound screening for uterine fibroids in U.S. for women aged 25-54 years was cost-effective and cost-saving. Study at a GlanceO_ST_ABSA. Why was this study conducted?C_ST_ABSO_LITo evaluate whether annual ultrasound screening for fibroids in women aged 25-54 years in the U.S. is cost-effective. C_LI B. What are the key findings?O_LIAnnual ultrasound screening beginning at 25 years was both cost-effective and cost-saving, with an ICER of -$56,605.631/QALY for women in the US. C_LIO_LIScreening resulted in potential savings of $1,169 billion for US healthcare payers and 20.7 million QALYs for U.S. women. C_LI C. What does this study add to what is already known?O_LIAnnual ultrasound screening for fibroids is not only cost effective but also cost saving, highlighting its potential to reduce diagnostic delays and enable earlier, less invasive interventions. C_LIO_LIThe results support development and implementation of fibroid screening guidelines. C_LI

ObjectiveTo evaluate modifiable antepartum and intrapartum factors associated with nulliparous, term, singleton, vertex (NTSV) cesarean delivery and to model risk stratified induction timing strategies that minimize cesarean risk across maternal risk profiles. Study DesignThis retrospective cohort study included all NTSV deliveries at a tertiary care center from January 2015 through August 2025 (overall cohort n=10,525; limited risk cohort n=5,663). Machine learning identified key predictors of cesarean delivery, with maternal age and pre pregnancy body mass index (BMI) used to define low, moderate, and high risk strata. Logistic regression estimated the association between induction and cesarean delivery, and a Monte Carlo simulation compared elective induction at 39, 40, or 41 weeks versus expectant management to 42 weeks within each stratum. ResultsCesarean delivery occurred in 20.1% of the overall cohort and 19.0% of the limited risk cohort, with a U shaped relationship between gestational age and cesarean risk and lowest rates at 38-39 weeks. Induction was associated with higher cesarean rates than spontaneous labor in both cohorts (overall: 24.1% vs. 17.1%; limited risk: 22.9% vs. 15.7%) after adjustment for age, BMI, and gestational age. No single induction policy minimized cesarean risk across all strata. For high risk patients (age >=35 years and BMI >=35), induction at 39 weeks yielded the lowest modeled cesarean rate, whereas later delivery (40 to 41 weeks or expectant management to 41 weeks) was favored for low and moderate risk patients. A universal 39 week induction policy for low and moderate risk strata modestly increased modeled cesarean rates, adding an estimated 46 cesarean deliveries. ConclusionGestational age at delivery and induction strategy are key modifiable determinants of NTSV cesarean delivery, but optimal timing varies by maternal age and BMI risk profile, supporting risk stratified rather than universal 39 week induction policies.

Introduction The link between Human Papillomavirus (HPV) and cancer is well-established. In Singapore, bivalent HPV vaccines are subsidised for females, but not males. Economic analysis of HPV vaccination has generally assessed the costs to the health system, but this may not be as relevant to individual decision-making as potential lost income. We estimated the impact of bivalent HPV 16/18 vaccination on sick leave, unemployment, and premature mortality as a function of age and sex to understand the broader impact of HPV-related cancers. Methods We developed a population-level economic model to estimate lifetime income losses by diagnosis age, sex and cancer type. We applied sex- and cancer-specific Cox regressions to the Singapore Cancer Registry for annual predicted survival from 1992 to 2022. These were combined with census and employment data to estimate HPV-associated income losses in Singapore. Attributable fractions and vaccine effectiveness data for HPV 16/18 from the literature were used to estimate the effectiveness of bivalent HPV vaccination. Structural sensitivity analysis examined the role of 80% population coverage conferring herd immunity. Results The registry contained 17,294 individuals with an HPV-associated cancer diagnosis. Lost income was greatest for cervical cancer due to its high prevalence, however the losses per diagnosis were highest for oropharyngeal cancer. Bivalent HPV vaccination led to income benefits of $SGD1,397 [$895 to $1,838] in girls and -$62 [-$76 to -$48] in boys. A gender-neutral HPV vaccination of 80% of 15-year-old Singaporeans, conferring herd immunity, would have lifetime income protective benefits of $24.4m [$14.2m, $33.7m] per cohort, a five-fold return on investment. Conclusions In addition to avoiding healthcare costs and lost quality of life, parents should consider vaccination as a means of avoiding potential income losses. A national policy of gender-neutral HPV vaccination could deliver substantial income protection due to both individual vaccine protection and herd immunity.

Objective: To externally validate a risk stratified delivery timing model for nulliparous, term, singleton, vertex (NTSV) cesarean reduction using national data. Design: Population based cohort study of NTSV births in US National Vital Statistics System (NVSS) natality files, 2020 to2024, using logistic regression for cesarean predictors and risk stratified Monte Carlo simulation (10,000 iterations per strategy and risk group) to evaluate delivery timing policies. Setting: All live births in the US recorded in the NVSS natality files. Participants: NTSV patients with term (37+ weeks) pregnancies and complete gestational age and delivery mode data (N=5 776 412). A sensitivity cohort excluded pre 39 week deliveries and pregnancies with preexisting diabetes or hypertension. Exposures: Delivery timing strategies defined by gestational age and labor onset (elective induction at 39, 40, or 41 weeks, or expectant management to 42 weeks), evaluated within maternal age and body mass index (BMI) risk strata (low: age <35 and BMI <30; moderate: age > 35 or BMI > 30; high: age > 35 and BMI > 35). Main Outcomes and Measures: Primary outcome was cesarean delivery, measured as the proportion of deliveries completed by cesarean across gestational ages, labor onset types, and age BMI strata. Secondary outcomes included gestational age specific cesarean rates, area under the receiver operating characteristic curve (AUC) for cesarean prediction, and simulated mean cesarean rates with 95% simulation intervals under four delivery timing strategies within each risk group. Results: The overall NTSV cesarean rate was 26.4%. Cesarean Rates were U shaped across gestational ages, with the lowest rate at 38 weeks (24.9%) and higher rates at 37 weeks (29.8%) and 41 to 42 weeks (28.1 to 28.5%). Risk group distribution was 64.9% low, 33.7% moderate, and 1.4% high. Model AUC was 0.65. Induction had higher cesarean rates than spontaneous labor (29.3% vs 24.2%; odds ratio 1.30, 95% confidence interval 1.29 to 1.30). Monte Carlo simulation favored induction at 39 weeks for high risk patients (59.3%) and expectant management to 41 to 42 weeks for low risk patients (19.1%). Conclusions and Relevance: A risk stratified NTSV labor management model showed external validity in 5.8 million US births and consistently identified risk-specific timing strategies that lowered cesarean rates, supporting individualized delivery timing policies.

ObjectiveTo retrospectively validate an electronic health record (EHR) implementation of the patient-initiated PreMA screener and compare its association with severe maternal morbidity (SMM) outcomes against established obstetric comorbidity indices. MethodsWe conducted a retrospective observational study using UCSF (single center) and UC-wide (multi-center) de-identified EHR data, identifying live-birth deliveries with documented preconception data. PreMA and established comorbidity index (Bateman and Leonard) scores were computed from preconception diagnoses, standardized to z-scores, and modeled as continuous predictors of SMM and non-transfusion SMM (NT-SMM) using logistic and Poisson regression models, with stratified analyses by race, ethnicity, and neighborhood deprivation. To examine the relationship between individual PreMA questionnaire domains and outcomes, we used adjusted Poisson regression to estimate the association of each domain with SMM and NT-SMM. ResultsAcross both cohorts, higher standardized PreMA, Bateman, and Leonard scores were consistently significantly associated with increased risk of SMM and NT-SMM, with relative risk estimates generally in the [~]1.2-1.4 range per standard deviation (adj. p < 0.001), and similar magnitude across indices and cohorts. Significant associations persisted across racial, ethnic, and socioeconomic, and item-level analyses suggested heterogeneity across PreMA domains, with cardiovascular domains showing the strongest adjusted associations. ConclusionAn EHR-derived PreMA score demonstrated robust, generalizable associations with severe maternal morbidity outcomes comparable to established clinician-facing indices, supporting PreMAs validity as a scalable, patient-centered preconception risk assessment tool.

Objectives: Influenza is a widespread acute respiratory illness posing a major public health challenge for both the National Health Service (NHS) and society, particularly among older adults. This study aimed to assess the cost-effectiveness of high-dose quadrivalent vaccine (HD-QIV) versus adjuvanted quadrivalent vaccine (aQIV) in older adults in Spain. Methods: Public health and economic benefits were evaluated using a decision-tree model considering influenza cases, GP and ED visits, hospitalizations, and influenza-related mortality. Deterministic and probabilistic sensitivity analyses addressed epidemiological and economic uncertainties. Results: From a societal perspective, HD-QIV prevented 54,039 influenza cases, 7,733 GP consultations, 1,585 ED visits, 27,398 episodes of hospitalization due to cardiorespiratory events over a single influenza season and 1,203 deaths compared to aQIV when vaccinating adults [&ge;]65 years old in Spain, resulting in 14,316 LYs and 12,440 QALYs gained over a lifetime horizon. The reduction in health outcomes outweighed the increase in vaccination costs, translating to a reduction in total costs with HD-QIV compared to aQIV. Therefore, vaccinating older adults in Spain with HD-QIV instead of aQIV was a dominant strategy when evaluating hospitalizations due to respiratory and cardiovascular events. HD-QIV remained dominant from a NHS perspective. Sensitivity analyses confirmed the robustness of the model. Conclusions: This analysis showed that vaccinating older adults in Spain with HD-QIV instead of aQIV would reduce influenza cases, GP and ED visits, hospitalizations, deaths, and associated costs, and thus it should be the strategy of choice in a situation of budgetary constraints from either a societal or an NHS perspective.

Objective: To develop and validate a multivariable prediction model and clinically actionable risk score for vaginal birth after cesarean (VBAC) success using machine learning, and to integrate neonatal morbidity outcomes into a decision-analytic framework for trial of labor after cesarean (TOLAC) counseling. Methods: We performed a retrospective cohort study of 1,418 consecutive TOLAC cases at a single tertiary care center in California from 2019 through 2025. Multivariable logistic regression and four machine learning algorithms (logistic regression, random forest, gradient boosting, extreme gradient boosting) were trained using 5-fold stratified cross-validation. A cumulative risk score (negative 1 to 7 points) was constructed from independently significant predictors. Neonatal intensive care unit (NICU) admission rates and uterine rupture rates were evaluated across risk strata. Results: The overall VBAC rate was 76.7% (1,087/1,418). Penalized logistic regression achieved the highest cross-validated AUC (0.71, 95% CI 0.67 to 0.75). A parsimonious multivariable logistic model used for score derivation had an AUC of 0.70 (95% CI 0.67 to 0.73). Independent predictors of failed TOLAC included induction of labor (adjusted odds ratio [aOR] 1.93, 95% CI 1.48 to 2.52), hypertensive disorders (aOR 1.60, 95% CI 1.19 to 2.15), diabetes mellitus (aOR 1.71, 95% CI 1.19 to 2.47), obesity (body mass index [BMI] 30 or greater; aOR 1.46, 95% CI 1.11 to 1.90), maternal age of 40 years or older (aOR 1.49, 95% CI 0.89 to 2.50), and gestational age of 41 weeks or greater (aOR 2.22, 95% CI 1.40 to 3.52). Prior vaginal delivery was independently protective (aOR 0.37, 95% CI 0.28 to 0.48). The cumulative risk score stratified VBAC success from 89.1% (score negative 1) to 37.8% (score 4 or higher). NICU admission rates increased concordantly from 31.7 to 200.0 per 1,000 across risk strata negative 1 through 4 or higher (Spearman rho 0.94, P for trend = .005). Uterine rupture occurred in 28 cases (1.97%) and was associated with severe maternal morbidity (10.7% vs 0.7%; odds ratio 16.56, P < .001) but was not predicted by any antepartum risk factor. Exclusion of patients with risk scores of 3 or higher (11.3% of the cohort) improved overall VBAC success to 80.0% (P = .04) and reduced NICU rates to 66.0 per 1,000. Conclusion: A machine learning to derived cumulative risk score incorporating prior vaginal delivery as a protective factor identifies TOLAC candidates with poor VBAC prognosis and elevated neonatal morbidity, providing an evidence-based tool for individualized delivery counseling. Uterine rupture remains unpredictable by antepartum characteristics.

Introduction Data on bloodstream infections (BSI) indicate a growth in incidence over time. This analysis utilised national data from England and the best available United States (US) evidence to predict BSI incidence over the years 2025 to 2029. The analysis utilised evidence on the cost-effectiveness of molecular rapid diagnostic tests (mRDT) to estimate the cost and mortality associated with BSI, and the potential for increased use of mRDT to save lives. Methods Data on BSI incidence by age group and sex for England in 2017 and the US (Minnesota) for 2003 to 2005 were combined with demographic projections over the years 2025 to 2029 to estimate the number of BSIs. Published costs and mortality associated with BSI, according to the method of identification of the pathogen, were used to estimate the lives saved and the cost impact of widespread use of mRDT in England and the US. Results BSI cases in England and the US are predicted to total 1.02 million and 6.24 million over the years 2025 to 2029, associated costs are GBP14.6 million and $221 million, respectively. Expanding the use of mRDT would save 2,219 and 7,554 lives in England and the US, respectively, over a 5-year period and would reduce healthcare expenditure in both countries. Conclusion There is a compelling argument to increase the uptake of mRDT to improve patient outcomes. This analysis demonstrates that expanded mRDT adoption can significantly reduce BSI burden, saving over 9,700 lives and decreasing healthcare expenditure in both countries.

Objective: To externally validate, at the national level, a cumulative risk score for vaginal birth after cesarean (VBAC) success and neonatal morbidity derived from single center data. Methods: We conducted a population based cohort study of all trial of labor after cesarean (TOLAC) attempts among term, singleton deliveries recorded in the Centers for Disease Control and Prevention natality files, 2020 to 2024 (N=477,693). The cumulative risk score (range - 1 to 7 points) incorporated body mass index (BMI) 30 or greater (+1), BMI 40 or greater (+1), induction of labor (IOL; +1), diabetes mellitus (+1), hypertensive disorder (+1), maternal age 40 years or older (+1), gestational age 41 weeks or greater (+1), and prior vaginal delivery (-1). VBAC success rates and neonatal intensive care unit (NICU) admission rates were evaluated across risk strata. Results: The overall VBAC rate was 73.3% (350,340/477,693). The cumulative risk score demonstrated a monotonic relationship with VBAC success: score -1, 90.5%; score 0, 76.4%; score 1, 69.4%; score 2, 62.2%; score 3, 55%; and score 4 or higher, 44.8%. NICU admission rates increased concordantly from 43.8 to 111.1 per 1,000 across strata. Prior vaginal delivery was the strongest individual predictor (VBAC 86.4% vs 62.5%). VBAC rates and TOLAC volume were stable across 2020 to 2024. Conclusion: The cumulative risk score derived from single center data was externally validated in a national cohort of 477,693 TOLAC attempts. The monotonic dose-response relationship between risk score and both VBAC success and NICU admission was confirmed, supporting the use of this score for individualized TOLAC counseling.

Background: In Burkina Faso, typhoid fever remains a major public health concern, with a high incidence among children younger than 15 years of age. To address this burden, the country introduced typhoid conjugate vaccine in January 2025 through a national vaccination campaign reaching children aged 9 months to 14 years. This study aimed to estimate the cost of typhoid conjugate vaccine delivery during the national campaign and to identify the main cost drivers across different administrative levels. Methods: We conducted a cross-sectional, retrospective costing study using a microcosting approach from the government perspective. We collected data from fifty health facilities, eight health districts, five health regions, and the national level. Financial and economic costs were estimated for each level, excluding vaccine and syringe costs. All costs were converted to 2024 USD using the official exchange rate. Findings: Vaccinators administered a total of 10.5 million typhoid conjugate vaccine doses. The average financial cost per dose was $0.47 (95% CI: $0.39-$0.51), and the economic cost was $2.16 (95% CI: $1.71-$2.56). Human resources and per diem payments were the main contributors to costs. Costs varied by geography, delivery strategy, and security context, with higher costs observed in rural and conflict-affected areas. The mobile-temporary posts strategy had the highest economic cost per dose ($2.02; 95% CI: $1.64-$2.40), while the fixed strategy had the highest financial cost per dose ($0.41; 95% CI: ($0.32-$0.49). Conclusion: The financial cost per dose remained within Gavi, the Vaccine Alliance's operational support range. The observed cost variations highlight the need for targeted funding and enhanced logistical support to ensure equitable access, particularly in rural and insecure areas. This study provides evidence to inform future vaccination campaigns and supports decision-making for typhoid conjugate vaccine introduction in other countries in the region.

BackgroundKCNT1-related disorders are a rare, severe neurogenetic disorder associated with early-onset, treatment-resistant seizures and significant developmental comorbidities. Currently there are no treatment-modifying therapeutics for this condition, and the condition necessitates complex, lifelong care that places a profound financial strain on affected families and healthcare systems. However, data quantifying this economic burden is sparse. ObjectiveTo evaluate the annual cost burden of KCNT1-related disorders in the United States using both caregiver-reported expenditures and electronic medical record (EMR) data, providing a comprehensive analysis of direct, indirect, and out-of-pocket expenses. MethodsA retrospective cohort analysis was conducted using two complementary data sources. In 2025, 34 U.S-based. caregivers from the KCNT1 Epilepsy Foundation registry completed a survey capturing insurance status, medical and non-medical expenses, and indirect costs. Separately, EMR data from 49 U.S.-based patients with KCNT1 variants were extracted from the Citizen Health database. Clinical services were mapped to CPT and HCPCS codes, and costs were calculated using Medicare fee schedules and other publicly available datasets. ResultsCaregiver-reported data revealed that all respondents possessed some form of insurance coverage, primarily through private insurance purchased independently or through their employer, or Medicaid. Nearly half of respondents (18/34) experienced financial hardship, citing high out-of-pocket expenses, medical debt, and loss of income due to caregiving responsibilities, and twelve percent of respondents delayed treatment due to financial strain (n=4). The estimated mean total annual medical cost per family--including direct, indirect, non-medical, and non-covered expenses--ranged from $355,474 to $797,727, based on upper and lower bounds of response categories from 10 respondents. EMR analysis, which only reported on direct medical costs, revealed that average first-year direct medical costs reached $154,389 per patient based on the records from 49 patients. This cost was primarily driven by hospitalizations, medications, and therapeutic procedures. Based on EMR data, direct medical costs declined once the patients reached two years of age and stabilized in subsequent years. Hospitalizations remained the most substantial cost contributor regardless of the age of the patient. ConclusionKCNT1-related disorders imposes a substantial economic burden on families and healthcare systems, particularly in the first year after diagnosis. This study highlights the need for rapid diagnostic procedures, targeted therapies, improved insurance coverage, and legislative support for families managing rare, high-burden conditions. Findings provide essential cost data to support drug development, healthcare planning, and rare disease policy reform. SignificanceThis is the first U.S.-based study to quantify both medical and non-medical costs associated with KCNT1-related disorders using combined caregiver and EMR data. The results highlight the urgency of disease-modifying treatments and equitable access to care, informing clinical trials and advocacy for systemic healthcare support.