Introduction The onset of febrile neutropenia (FN) demands dose reduction and usually temporary halting of chemotherapy, which could then affect the outcome of cancer treatment. In this study, we wanted to quantify the drugs used in treating febrile neutropenic episodes, the costs incurred as a result, and the outcomes of these episodes. Methods The study was a prospective observational study. Patients of either sex, of any age, and diagnosed with high-risk FN following cancer chemotherapy and hospitalized during the period of study were included. A total of 46 patients with 50 episodes of FN were enrolled. Data were collected from the department database and daily clinical notes and were entered into a pre-designed proforma. The drugs prescribed were classified as antibiotics and supportive medications. The drug cost of each episode was then calculated. The data were analysed using descriptive statistics. Results The mean age of participants was 26.66 years, with a median length of hospital stay of 10 days. This provides an estimate of the drug-related costs. A total of Rs. 8,21,731 was spent on drugs for the management of 50 episodes, and the average cost of an episode was Rs. 16,434. Of the total cost, Rs. 7,00,300 (85.22%) was spent on antimicrobials. Conclusion Considering the complexities of medical decision-making and quality of care, the role of cost needs to play a major role in therapeutic options. There is a need to develop value-based policies to achieve the best clinical outcomes while accounting for cost-effectiveness and polypharmacy.
Partial nephrectomy is increasingly favored for small renal masses due to its renal function-preserving benefits. This study compared contemporary utilization patterns, perioperative outcomes, and hospital costs of robotic-assisted (RAPN), laparoscopic (LAPN), and open partial nephrectomy (OPN) among U.S. patients with renal cancer. Using the 2016–2019 National Inpatient Sample, renal cancer patients undergoing RAPN, LAPN, or OPN based on ICD-10-CM/PCS codes were identified. Patient demographics, comorbidities, hospital characteristics, length of stay (LOS), perioperative complications, and hospital costs, were summarized by surgical approach. Regression analyses adjusted for patient- and hospital-level covariates were used to compare perioperative outcomes, LOS, and costs across procedures. An estimated 89,290 partial nephrectomies were identified (mean age 59.4 years; 60.4% male; 68.9% white). RAPN was the most common approach (63.4%), followed by OPN (22.6%) and LAPN (14.0%). Median hospital costs were lowest for LAPN ($14,627), compared with RAPN ($15,187) and OPN ($15,364). Both RAPN and LAPN were associated with lower odds of perioperative complications compared with OPN (RAPN: OR 0.48, 95% CI 0.43–0.55; LAPN: OR 0.51, 95% CI 0.43–0.61). RAPN was additionally associated with lower odds of blood transfusion, in-hospital mortality, and shorter LOS. After adjustment, hospital costs for RAPN and LAPN were not statistically significantly different from those for OPN. RAPN represents the predominant minimally invasive approach for partial nephrectomy in contemporary U.S. practice. Minimally invasive techniques offer clear clinical advantages over open surgery, with RAPN demonstrating more favorable intraoperative outcomes than LAPN. Future research should assess long-term functional, oncologic, and economic outcomes. The online version contains supplementary material available at 10.1007/s00345-026-06329-w.
Simulation models inform health policy decisions by integrating data from multiple sources and forecasting outcomes when there is a lack of comprehensive evidence from empirical studies. Such models have long supported health policy for cancer, the first or second leading cause of death in over 100 countries. Discrete-event simulation (DES) and Bayesian calibration have gained traction in the field of decision science because they enable flexible modeling of complex health conditions and produce estimates of model parameters that reflect real-world disease epidemiology and data uncertainty given model constraints. This uncertainty is then propagated to model-generated outputs, enabling decision-makers to assess confidence in recommendations and estimate the value of collecting additional information. However, there is limited end-to-end guidance on structuring a DES model for cancer progression, estimating its parameters using Bayesian calibration, and applying the calibration outputs to policy evaluation. To fill this gap, we introduce the DES Modeling Framework for Cancer Interventions and Population Health in R (DESCIPHR), an open-source codebase integrating a flexible DES model for the natural history of cancer, Bayesian calibration for parameter estimation, and an example application of screening strategy evaluation. To illustrate the framework, we apply DESCIPHR to calibrate bladder and colorectal cancer models to real-world cancer registry targets. We also introduce an automated method for generating data-informed parameter prior distributions and increase the functionality of a neural network emulator-based Bayesian calibration algorithm. We anticipate that the adaptable DESCIPHR modeling template will facilitate the construction of future decision models evaluating the risks and benefits of health interventions.
Cyclosporine ophthalmic emulsion 0.05% (CsA 0.05%) and cyclosporine ophthalmic solution 0.09% (CsA 0.09%) are approved to increase tear production in dry eye disease (DED). We investigated the effect of CsA 0.09% on DED signs and symptoms in patients whose disease was inadequately controlled on CsA 0.05%. In this Phase 4, single-arm, open-label study, adults with DED administered 1 drop of CsA 0.09% in both eyes twice daily for 12 weeks. Patients were ≥ 18 years of age with a history and clinical diagnosis of DED for ≥ 3 months, which was not adequately controlled by treatment with CsA 0.05%. The primary efficacy endpoints were mean changes from baseline in total corneal fluorescein staining (CFS) and modified Symptom Assessment iN Dry Eye (mSANDE) scores at Week 12. Secondary efficacy endpoints included mean changes from baseline in total conjunctival staining score, central CFS score, tear osmolarity, Schirmer test score, and frequency of artificial tear use at Week 12, and patient treatment preference at Week 12. Adverse events (AEs) were monitored. The intent-to-treat population comprised 124 patients (mean age, 65.6 years). The mean changes from baseline in total CFS and mSANDE scores were statistically significant at Weeks 4, 8, and 12 (P < 0.0001 for all). At Week 12, statistically significant improvements from baseline were also noted for total conjunctival staining score, central CFS score, Schirmer test score, and artificial tear use frequency (P ≤ 0.0029), and 69.4% of patients preferred CsA 0.09%. Most AEs were mild. Treatment with CsA 0.09% elicited statistically significant improvement from baseline in DED signs and symptoms from Weeks 4 to 12 in patients inadequately controlled on CsA 0.05%. Overall, CsA 0.09% was well tolerated. The findings from this study suggest that switching from CsA 0.05% to CsA 0.09% may improve signs and symptoms in patients with DED. In this study, patients with dry eye who were still experiencing symptoms while receiving treatment with cyclosporine ophthalmic emulsion 0.05% were switched to cyclosporine ophthalmic solution 0.09% (CsA 0.09%) for 12 weeks. Both formulations use the anti-inflammatory agent cyclosporine, but CsA 0.09% uses a slightly higher concentration that is dissolved into a solution rather than emulsified in an oil like some other dry eye drops. Patients were assessed using eye stains and questionnaires before switching to CsA 0.09%, which served as the baseline for each patient. Patients were then re-examined and completed another questionnaire regarding their dry eye symptoms every 4 weeks during the 12 weeks they received CsA 0.09%. As early as Week 4, patients on average had improvements in dry eye staining and symptom management (based on their questionnaire scores), which were associated with better control of their dry eye symptoms. At the end of the study, 69% of patients preferred CsA 0.09% over their previous eye drops, and CsA 0.09% was well tolerated by patients and was associated with mostly minor ocular side effects; eye irritation after applying the eye drops was reported most frequently. Taken together, these results suggest that treating dry eye early with CsA 0.09% may be beneficial, and some patients who struggle to adequately control their dry eye symptoms with other dry eye drops may benefit from switching their treatment to CsA 0.09%.
Inhaled corticosteroid (ICS)-long-acting β-agonist (LABA) inhalers are generally considered therapeutically equivalent when treating chronic obstructive pulmonary disease (COPD). However, metered-dose inhalers in the class are associated with substantially higher greenhouse gas emissions than dry powder formulations, and studies have raised questions about potential intraclass differences in clinical outcomes among patients receiving ICS-LABAs. To analyze COPD exacerbations and pneumonia hospitalizations associated with once-daily fluticasone furoate-vilanterol dry powder inhalers, twice-daily fluticasone propionate-salmeterol dry powder inhalers, and twice-daily budesonide-formoterol metered-dose inhalers in adults with COPD. This cohort study was conducted using longitudinal commercial claims data of US adults aged 40 years or older with COPD. Patients were 1:1 pairwise propensity score matched into 3 cohorts: (1) new users receiving fluticasone furoate-vilanterol vs budesonide-formoterol between January 1, 2014, and February 29, 2024; (2) new users receiving fluticasone furoate-vilanterol vs fluticasone propionate-salmeterol between January 1, 2014, and February 29, 2024; and (3) new users receiving fluticasone propionate-salmeterol vs budesonide-formoterol between January 1, 2007, and February 29, 2024. Receipt of a once-daily fluticasone furoate-vilanterol dry powder inhaler (Breo Ellipta; GSK), twice-daily fluticasone propionate-salmeterol dry powder inhaler (Advair Diskus; GSK), or twice-daily budesonide-formoterol metered-dose inhaler (Symbicort; AstraZeneca). The primary outcomes were first moderate or severe COPD exacerbation and first pneumonia hospitalization. Hazard ratios and 95% CIs were estimated using Cox proportional hazards regression models. The cohorts included 38 070 matched pairs of patients receiving fluticasone furoate-vilanterol vs budesonide-formoterol (58.8% women; mean [SD] age, 71.0 [9.0] years), 20 471 matched pairs of patients receiving fluticasone furoate-vilanterol vs fluticasone propionate-salmeterol (58.3% women; mean [SD] age, 69.9 [9.2] years), and 55 627 matched pairs of patients receiving fluticasone propionate-salmeterol vs budesonide-formoterol (56.2% women; mean [SD] age, 68.3 [9.0] years). Patients receiving fluticasone furoate-vilanterol had a 9% lower risk of moderate or severe COPD exacerbations compared with those receiving budesonide-formoterol (hazard ratio [HR], 0.91 [95% CI, 0.88-0.94]; number needed to treat [NNT] = 40) and a 6% lower risk compared with those receiving fluticasone propionate-salmeterol (HR, 0.94 [95% CI, 0.89-0.98]; NNT = 40). The risk of moderate or severe COPD exacerbation was similar for patients receiving fluticasone propionate-salmeterol and budesonide-formoterol (HR, 0.98 [95% CI, 0.95-1.01]). No differences were observed in the risk of pneumonia hospitalization across the 3 cohorts (fluticasone furoate-vilanterol vs budesonide-formoterol: HR, 1.03 [95% CI, 0.96-1.11]; fluticasone furoate-vilanterol vs fluticasone propionate-salmeterol: HR, 0.93 [95% CI, 0.85-1.03]; and fluticasone propionate-salmeterol vs budesonide-formoterol: HR, 1.04 [95% CI, 0.98-1.10]). In this cohort study of new ICS-LABA users with COPD, once-daily dry powder fluticasone furoate-vilanterol inhalers were associated with slightly improved clinical outcomes compared with twice-daily metered-dose budesonide-formoterol inhalers and twice-daily dry powder fluticasone propionate-salmeterol inhalers. Further studies are needed to explore potential intraclass differences among inhalers used to treat COPD.
In Medicare, out-of-pocket spending for insulin was capped at $35 per month for some patients in 2021 and for all patients in 2023. However, independent evaluations of the federal cap and clinical outcomes are lacking. To measure changes in patient spending, insulin use, and health outcomes associated with the $35 monthly insulin out-of-pocket cap. This cohort study used an interrupted time-series analysis of data from Medicare Part D beneficiaries with type 2 diabetes (T2D) included in the IQVIA national longitudinal open claims database from 2019 to 2023; a subset of patients had linked data from ambulatory electronic medical records. The analysis was performed between January and July 2025. Implementation of the $35 monthly insulin out-of-pocket cap to some beneficiaries in January 2021 and all beneficiaries in January 2023. Outcomes included mean quarterly insulin out-of-pocket spending, mean daily units of insulin, mean hemoglobin A1c level, and incidence rates of severe hypoglycemia resulting in hospitalizations or emergency department visits. Changes were assessed using segmented regression with generalized estimating equations, adjusted for patient age and sex and within-year seasonal variation. The study included 4.8 million patients, with a median quarterly cohort size of 1 393 402 patients (range, 1 261 976-1 475 460). In the first quarter of 2019, the baseline cohort included 707 416 males (51.1%), with 711 075 patients (51.3%) aged 65 to 74 years. Mean quarterly insulin out-of-pocket spending was $192.66 (95% CI, $192.63-$192.68) at baseline and declined by $47.90 (95% CI, -$48.95 to -$46.84) in 2021 and by another $58.59 (95% CI, -$59.91 to -$57.27) in 2023. Among all patients with T2D, mean daily insulin use was 12.86 (95% CI, 12.86-12.87) units at baseline and increased by 0.23 (95% CI, 0.15-0.31) units in 2023. Among a subset of 207 197 patients with linked electronic medical record data, mean hemoglobin A1c level was 7.28% (95% CI, 7.28%-7.28%) at baseline and decreased by 0.06% (95% CI, -0.08% to -0.03%) after 2023. There were corresponding modest increases in rates of severe hypoglycemic events. In this cohort study, a $35 monthly insulin out-of-pocket cap was found to be associated with significantly lower insulin out-of-pocket spending, increased access to insulin, and decreased blood glucose levels among Medicare beneficiaries with T2D. These findings suggest federal cost-sharing policies could improve access and adherence to essential medications in diabetes and other chronic diseases.
Proton therapy is an alternative treatment to photon therapy in head and neck cancer. The Normal Tissue Complication Probability (NTCP) model assists in the patient selection process. This study explores how health technology assessment (HTA) recommendations in lower-income European countries (LIECs) in head and neck cancer can be supported by transferring the NTCP model. Through 2 workshops in November 2022 and May 2023, the scope of transferability recommendations was established for the head and neck cancer case study of the HTx project. HTA experts from LIECs and HTx consortium representatives reviewed draft recommendations at a final transferability workshop in November 2023. Experts anonymously voted on the main challenges of transferring the NTCP model to LIECs and ranked these by importance. Finally, an open discussion took place about potential solutions for overcoming the main challenges. Main challenges of transferring the NTCP model to LIECs include lack of available local data, differences in patient pathways, and shortage of HTA experts. Workshop participants agreed that the NTCP model is an improvement to current standard HTA methods. Multiple key recommendations were formed, including that dissemination of real-world data and real-world evidence should be gold standard, coupled with a wide collaboration across stakeholders, and that consideration of transferability aspects could help LIECs when adapting novel methods. According to a multinational panel of experts, the NTCP model is an improvement over current HTA methods. To overcome challenges of its adoption in LIECs, 5 key recommendations were formulated.
With cardiac myosin inhibitors emerging as a novel pharmacological option instead of septal reduction therapies (SRT) in obstructive hypertrophic cardiomyopathy (HCM), contemporary data on national long-term outcomes after SRT are needed. In this nationwide cohort study from 2015 to 2021, patients with obstructive HCM undergoing SRT (surgical myectomy or transcoronary ablation of septal hypertrophy) were 1:8 propensity score-matched with non-obstructive HCM patients or surgical controls undergoing appendectomy without heart disease in recent records. As assessed in time-to-event analyses, the primary outcome was a composite of all-cause mortality after discharge and rehospitalization for heart failure. After matching, 125 patients with obstructive HCM hospitalized for SRT were compared to 743 patients hospitalized with non-obstructive HCM. The incidence rate (IR) of the primary outcome was lower in the SRT group {12.62 vs. 74.86 per 1000 patient-years (py); hazard ratio (HR), 0.17 [95% confidence interval (CI), 0.07-0.42]; median follow-up 31 months}. In the second comparison, 126 patients with obstructive HCM undergoing SRT were matched to 560 surgical controls without heart disease undergoing laparoscopic appendectomy. The IR of the primary outcome after SRT was comparable to that of surgical controls without heart disease [12.61 vs. 8.09 per 1000 py; HR, 1.53 (95% CI, 0.56-4.18); median follow-up 41 months]. In this nationwide cohort study, SRT was associated with a lower incidence of all-cause mortality after discharge and rehospitalization for heart failure compared to patients hospitalized with non-obstructive HCM, with an incidence comparable to surgical controls without heart disease.
Bevacizumab was approved for first-line treatment of metastatic colorectal cancer (mCRC) in 2004. However, adding bevacizumab to treatment consistently fails to be cost-effective owing to modest response rates. Recently, the European Commission (EC) funded ANGIOPREDICT consortium ( www.angiopredict.com ) identified a link between bevacizumab treatment response and intermediate-to-high chromosomal instability (CIN) in mCRC. Thus, the objective of the current study was to compare the cost-effectiveness of adding bevacizumab with first-line chemotherapy in the bevacizumab responsive CIN subtype across three European countries (Germany, Ireland and Spain) with varying costs of care and reimbursement policies. We developed an open-source health economic model to estimate cost-effectiveness. The ANGIOPREDICT cohort informed progression risks and cause-specific mortality. Health utilities and adverse events probabilities were obtained from the literature. Costs were derived from surveys of collaborating consortium hospitals in Germany, Ireland, and Spain that participated in the recently completed EC funded COLOSSUS translational study (ANGIOPREDICT successor initiative) and the literature. Sensitivity analyses included individual and simultaneous variation of input parameters from a priori defined distributions. Bevacizumab was not cost effective even at willingness-to-pay (WTP) thresholds that are appreciably higher than those considered realistic. The highest incremental cost-effectiveness ratio (ICER) was in Germany at €241,188 per quality-adjusted life year (QALY), while the lowest was in Ireland at €180,477 per QALY. All deterministic and probabilistic sensitivity analyses demonstrated that these results were robust. Even for patients with mCRC manifesting improved outcomes, adding bevacizumab to first-line chemotherapy is invariably not cost-effective in any of the countries examined. Variability in pricing, healthcare costs and WTP thresholds across countries did not commute this result.
Healthcare decision-making often assumes equal value for quality-adjusted life years (QALYs) across patient groups, yet societal preferences suggest that the value of a QALY may vary with characteristics such as age. Evidence indicates some willingness to prioritise child health gains, though findings are inconsistent. This study used person trade-off (PTO) to estimate the relative social value of different types of health gains for children and adolescents (aged 0-24 years) compared with adults. A representative Australian sample aged 16 years and above (n = 2098) completed an online survey comparing life extension and quality-of-life improvements for different ages. A 'chaining' approach tested response consistency, and logistic regression explored associations between PTO choices and respondent characteristics. Attitudinal questions and open text responses provided additional insights. PTO responses show that health gains for children and adolescents (4-24 years) are generally valued more highly than those for adults (age 40 or 55 years), with weights ranging from 1 to 1.3. For very young children, findings vary by health gain type: life extensions for infants (1 month or 2 years) are weighted lower, but pain alleviation is higher (weights ≥ 1.2). Qualitative and attitudinal data reveal diverse views, with many opposing age-weighting. Younger respondents and those with young children prioritise children more, while older and female participants preferred equal treatment. The relative value of child QALY gains varies by age of the child, by health gain type, and by adult comparison age. While alleviating children's pain is strongly supported (weights ≥ 1.2), overall views are polarised, highlighting the complexity of age-based prioritisation.
Patch insulin pumps are often treated as a single class, although fully disposable and semi-reusable designs differ in cost and waste. We evaluated real-world clinical, pharmacoeconomic, and environmental outcomes of a semi-reusable tubeless insulin pump (Microtech Equil™, referred as SR-TIP). Prospective, multicentre, open-label real-world study in adults with type 1 or type 2 diabetes transitioning from continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). Follow-up was 3 months. Primary endpoints were HbA1c non-inferiority and change in hypoglycaemic event frequency. Secondary endpoints included safety, device deficiencies, patient-reported outcomes (Diabetes Treatment Satisfaction Questionnaire, Device Assessment Questionnaire), monthly disposable treatment costs, and waste based on disposable component counts and material composition. Ninety-seven participants completed follow-up (CSII n = 79; MDI n = 18). HbA1c changes met non-inferiority criteria in both groups. Hypoglycaemic events decreased by 45% in CSII users and 86% in MDI users. Device-related adverse events were infrequent and mainly mild. Among participants previously using fully disposable tubeless pumps, mean monthly disposable treatment costs decreased by €108.6 (p < 0.001). The semi-reusable architecture eliminated routine disposal of batteries/electronic components and reduced overall waste. In routine care, a semi-reusable tubeless pump maintained glycaemic control while reducing hypoglycaemia and disposable costs versus fully disposable patch pumps, with measurable reductions in electronic waste. These data support value-based, sustainable diabetes technology adoption.
Health economic modelling integrates evidence from multiple sources and relies on transparency to support reimbursement decisions. Hyperlipidaemia is a major contributor to cardiovascular disease and is routinely evaluated within health technology assessment frameworks. This systematic review examines health economic models of hyperlipidaemia, evaluates the methodological approaches used in the model development and identifies opportunities to improve model quality and transparency. A systematic literature search was conducted in MEDLINE and Embase between 1987 and 2025 to identify hyperlipidaemia health economic models. Screening, data extraction and quality assessment were performed manually, and artificial intelligence (AI) software was used for additional checking, this was followed by conflict resolution. Findings are presented through narrative synthesis. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251043922). The review assessed key aspects of model structure including model type, type of hyperlipidaemia, population, hyperlipidaemia-related events, model outcomes, time horizon, software used and discounting approach. We assessed methodological quality through the Philips checklist, with a focus on model structure, data usage, the way in which studies addressed uncertainty through sensitivity analysis and model validation. A total of 154 unique model-based economic evaluations were identified, comprising 132 Markov models, 9 microsimulation models and 1 discrete event simulation. Most economic evaluations explored general hypercholesterolaemia in 138 studies, followed by familial hypercholesterolaemia in 23 studies, while lipoprotein(a) was investigated in two studies. Primary prevention was examined in 89 models, secondary prevention in 50 models and a combination of both in 15 evaluations. Overall methodological quality was assessed as high for models' structure and data usage; however, it was moderate for model consistency. Hyperlipidaemia models generally had transparent assumptions and a justified structure. However, current models often lack systematic data-selection practices to identify the most appropriate evidence for evaluation. Extensive uncertainty analysis and model validation were frequently absent in the assessed models. To support decision-making, model results should be displayed in an open-source format with publicly available code. Furthermore, patient values are rarely incorporated in current modelling practices, representing missed opportunities for patient-centred care.
BACKGROUND: The long-term use of beta blockers after myocardial infarction in patients with preserved ventricular function is debated. General practitioners (GPs) often decide whether to continue or discontinue long-term medications, yet little is known about how they apply evolving evidence to clinical prescribing decisions. OBJECTIVE: To assess whether GPs are willing to deprescribe beta blockers post myocardial infarction with preserved left ventricular function and to identify factors associated with deprescribing decisions. DESIGN: Cross-sectional online survey using case vignettes, conducted between July 2023 and October 2024 in primary care settings in 24 sites across 20 European countries. PARTICIPANTS: Practicing GPs recruited through convenience sampling at each site. MAIN MEASURES: The primary outcome was whether the GP chose to deprescribe beta blockers in the vignettes. Adjusted risk ratios for the association between GP characteristics and the decision to deprescribe were estimated using Poisson regression with generalized estimating equations and robust standard errors, accounting for clustering at the GP and country level. KEY RESULTS: 604 GPs participated in the survey (median [IQR] age, 44.0 [35.0-54.8] years; 364 [60.3%] female), 89.2% deprescribed beta blockers in at least one vignette. The likelihood of deprescribing increased with time since myocardial infarction (adjusted risk ratio [RR] = 1.28; 95% CI 1.21–1.36 after 5 years; RR = 1.78; 95% CI 1.66–1.90 after 10 years vs. 3 months) and with side effects (RR = 1.76; 95% CI 1.66–1.88). More years of clinical experience were associated with a lower likelihood of deprescribing (RR = 0.86; 95% CI 0.77–0.95 for most vs. least experienced). CONCLUSIONS: In this cross-national vignette study, most GPs were willing to deprescribe beta blockers after myocardial infarction in patients with preserved left ventricular function, particularly when time had passed and side effects were present. These findings suggest that GPs are open to applying evolving evidence on beta blocker discontinuation in clinical care.
We performed a cost-utility analysis, using prospectively gathered trial data, comparing two imaging strategies for localizing parathyroid adenomas in primary hyperparathyroidism (pHPT) to determine the most cost-effective approach. Additionally, we provide customizable open-source R-script enabling other centres to identify their optimal imaging strategy based on local diagnostic accuracy and cost data. An evaluation of the diagnostic accuracy was performed for five imaging modalities: first-line cervical ultrasound (cUS) and [99mTc]Tc-methoxy isobutyl isonitrile-single-photon-emission-computed- tomography/computed-tomography (MIBI SPECT/CT), and second-line [¹¹C]choline positron-emitting-tomography/CT (PET/CT), [¹¹C]methionine PET/CT, and 4 dimensional (4D)-CT. A decision-tree-model, constructed in R-studio, compared two diagnostic pathways: (1) The comparator pathway: a stepwise approach starting with cUS and MIBI SPECT/CT escalating to one of three second-line imaging modalities if needed, and (2) use of only one second-line imaging. Costs and quality-adjusted life years (QALYs) were evaluated across pathways, and cost-utility ratios (€/QALY) were calculated for a centre specific perspective with a 24-year time horizon based on life expectancy. In addition, to test the joint parameter uncertainty of the model, a probabilistic Monte-Carlo analysis was performed. One- and two-way sensitivity analyses were conducted to assess model robustness. [¹¹C]choline PET/CT had a total costs of €10,394 and a QALY gain of 16.66. In contrast, the current standard, cUS + MIBI SPECT/CT with, when necessary, second-line imaging, costs €10,907 and yields 16.63 QALYs. The incremental cost-utility ratio (ICUR) for [¹¹C]choline PET/CT was -€18,846/QALY, indicating dominance with lower cost and greater effectiveness. Sensitivity analyses showed that cost-effectiveness was most sensitive to variations in costs of [¹¹C]choline PET/CT. This centre-specific model supports first-line [¹¹C]choline PET/CT as a cost-effective first-line strategy for localization of parathyroid adenomas, depending on [¹¹C]choline PET/CT costs. Additionally, the provided cost-utility model, enables other centres to determine their optimal imaging strategy.
Despite evidence on the cost effectiveness of catheter ablation (CA) as a rhythm control strategy in patients with atrial fibrillation, CAs form a substantial share of medical resource consumption, raising questions about optimal timing and maximum CAs per patient. This study addresses these questions using a newly developed open source model integrating observational and clinical trial data. The objective was to estimate the cost effectiveness of rhythm control strategies including anti-arrhythmic drugs (AADs) and/or CA in different sequences from a societal perspective in the Netherlands. Time to atrial fibrillation symptom recurrence after a CA was estimated using parametric survival functions estimated on health insurance data (n = 24,286). Relative efficacy of CAs versus AADs was derived from meta-analyses, accounting for previous treatment exposure. Six treatment lines were modeled, incorporating AADs and CAs as rhythm control strategies. Medical and societal costs were included and the model had a lifetime time horizon. Model results were generated in 2024 Euros using Dutch input data with a cost-per-quality-adjusted life-year threshold of €20,000. For the probabilistic sensitivity analyses, we simultaneously varied all parameters across 1000 model runs with 5000 patients each. Treatment sequences including at least one CA were cost effective compared with only AADs. Catheter ablation costs are counterbalanced by reduced medical resource consumption in the years following CA. 51.6% of patients with first-line CA remain symptom free over a lifetime versus 6.9% with AADs. The most cost-effective strategy starts with CA, manages atrial fibrillation recurrences with AADs, and uses a maximum of three repeat ablations. Our model suggests that rhythm control with at least one CA is cost effective compared with only AADs in patients with atrial fibrillation requiring rhythm control. Within shared decision making, first-line CA, followed by AADs to manage atrial fibrillation recurrences, with a maximum of three repeat ablations, represents the most cost-effective strategy for patients with symptomatic atrial fibrillation requiring rhythm control.
Large language models (LLMs) are evolving rapidly and hold great promise for medical applications, yet benchmarking on real-world clinical data such as electronic health records remains limited. Most existing benchmarks rely on medical examination-style questions or PubMed-derived text, failing to capture the complexity of clinical practice, while others target specific application scenarios with limited generalizability. Here we present BRIDGE, a comprehensive multilingual benchmark comprising 87 tasks sourced from 59 real-world clinical data sources across 9 languages. It covers eight task types spanning the patient care continuum, including triage, information extraction, diagnosis, prognosis and billing coding, and involves 14 clinical specialties. We systematically evaluated 95 LLMs (including DeepSeek-R1, GPT-4o, Gemini and Qwen3) under multiple inference strategies. Results reveal substantial performance variation across model sizes, languages, natural language processing tasks and clinical specialties. Open-source LLMs can match proprietary models, while medically fine-tuned models built on older backbones often lag behind updated general-purpose LLMs. BRIDGE and its continuously updated leaderboard provide foundational resources and important references for evaluating and developing LLMs for real-world clinical text understanding.
Industry payments to clinicians influence prescribing, limiting use of lower-cost generics, and leading to nonadherence. This study of prescribing for multiple sclerosis examined whether payments from brand-name drug manufacturers were associated with prescribing of brand-name glatiramer and dimethyl fumarate after generics became available. This cross-sectional study used 2021-2022 Open Payments data and 2022-2023 Medicare Part D prescription data. Payments from Teva (glatiramer) and Biogen (dimethyl fumarate) were categorized as none, <$1,000, or ≥$1,000. The outcome was the proportion of brand-name prescriptions per clinician, categorized as low (<20%), medium (20%-79%), or high (≥80%). Associations were assessed using multinomial logistic regression, adjusting for prescriber type, prescription volume, and geographic region. Among 2,675 glatiramer and 2,138 dimethyl fumarate prescribers, 1,026 (38.4%) and 1,238 (57.9%) received payments, respectively. Receiving ≥$1,000 in payments was associated with a greater odds of high brand-name prescribing for glatiramer (adjusted odds ratio [aOR] 4.21, 95% CI 1.81-9.81, p < 0.001) and dimethyl fumarate (aOR 2.53, 95% CI 1.57-4.07, p < 0.001). Payments <$1,000 were also associated with higher brand-name prescribing. Payments to clinicians were associated with lower uptake of generic versions of 2 MS drugs, resulting in higher spending by patients and the US health care system.
Prior drug safety studies investigating the risk of neuropsychiatric events (NPEs) after montelukast initiation have been limited by methodological issues, including incomplete confounder control and unmeasured outcomes associated with completeness of structured data, as well as events recorded only in unstructured clinical notes. To examine the value associated with using linked claims and electronic health records (EHRs) (structured and unstructured data) while investigating the risk of any NPE among patients with asthma initiating montelukast compared with inhaled corticosteroids (ICSs). This retrospective cohort study used Oracle EHR Real-World Data linked to a national US claims dataset (July 1, 2015, to June 30, 2022) to identify patients aged 6 to 80 years with asthma newly initiating montelukast or ICSs. The data were analyzed between December 13, 2022, and August 2, 2024. The primary outcome of any NPE and covariates was assessed using the incremental addition of each data source: analysis 1, claims-only data; analysis 2, claims plus structured EHR data; and analysis 3, claims plus structured and unstructured EHR data. Cox proportional hazard regression models using propensity score-matched cohorts across data sources were used to examine the risk of any NPE by treatment initiation group. Among 109 076 patients (mean [SD] age at treatment initiation, 28.8 [20.5] years, 59.4% female), 39 665 (36.4%) initiated montelukast and 69 411 (63.6%) ICSs. Incidence rates per 100 person-years of the first postindex NPE increased with additional data sources for both montelukast and ICS users (analysis 1, 17.11 [95% CI, 16.86-17.36] vs 15.57 [95% CI, 15.34-15.80], respectively; analysis 2, 19.10 [95% CI, 18.83-19.38] vs 18.23 [95% CI, 17.97-18.50], respectively; analysis 3, 27.78 [95% CI, 27.43-28.13] vs 27.40 [95% CI, 27.06-27.75], respectively). Hazard ratios were attenuated across contributing data sources for analysis 1 (1.08 [95% CI, 1.05-1.11]), analysis 2 (1.04 [95% CI, 1.01-1.06]), and analysis 3 (1.01 [95% CI, 1.00-1.03]). This cohort study found that clinical information from linked claims and structured and unstructured EHR data was associated with enriched measurement of patient and disease characteristics and enhanced completeness of evidence vs claims data alone. The findings, however, did not differ substantially across the incrementally contributing data sources or from prior studies. Drug safety and effectiveness studies should integrate information using clinical notes from EHRs with consideration of potential limitations, challenges, and necessary validation processes.
The HD21 trial demonstrated efficacy and safety of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD) vs. bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) as frontline therapy for advanced-stage, classical Hodgkin lymphoma. This analysis evaluated the cost-effectiveness of BrECADD from a US healthcare payer perspective. Building upon a multicenter, randomized, open-label phase 3 HD21 trial (NCT02661503) that evaluated BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma patients, we constructed a Markov model with 3-week cycles over a 50-year horizon. The model's primary outcomes encompassed total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios, with all economic parameters discounted at 3.0% annually. Cost-utility analyses employed a willingness-to-pay threshold of $100,000 per QALY, supplemented by comprehensive sensitivity and scenario analyses to verify model robustness. Economic evaluation demonstrated that compared to eBEACOPP, the BrECADD regimen yielded an additional 2.24 QALYs at an incremental cost of $113,134.17, producing an ICER of $50,411.69/QALY, substantially below the $100,000 WTP threshold. One-way sensitivity analysis identified BrECADD drug acquisition costs and health state utility values as the predominant model drivers; all ICERs remained below the $100,000 WTP threshold across the plausible ranges of all parameters. Probabilistic sensitivity analysis indicated that at a willingness-to-pay threshold of $100,000 per QALY, BrECADD was cost-effective compared to eBEACOPP in 100% of 1000 Monte Carlo iterations. The cost-effectiveness acceptability curve demonstrated that BrECADD achieved a greater than 50% probability of being cost-effective at WTP thresholds above approximately $55,000 per QALY. BrECADD can be considered a cost-effective treatment versus eBEACOPP in treating advanced-stage, classical Hodgkin lymphoma in America. Not applicable.
Metabolic dysfunction-associated steatohepatitis (MASH) is defined by a buildup of fat in the liver and signs of inflammation and liver damage (fibrosis). Eventually, subjects with MASH may develop cirrhosis, leading to more serious consequences of decompensation, liver cancer, and liver failure. In this manuscript, a population-level burden-of-disease model for MASH in the USA is constructed that may form a novel framework to assess the value of new population-level diagnostic and treatment strategies for MASH as they emerge. We develop an underlying model of MASH, similar to published models in literature, nested within a population model. Using this model, we estimate the likely incidence of MASH at the stage at which it is most indolent and difficult to detect through calibration techniques and published prevalence of later disease stages. We then present a graphical analysis of disease burden, including disaggregating this burden by age and sex, and into the relative contribution of morbidity and mortality. From the model, we realised that MASH has a higher burden if acquired earlier in life, and the decade in which burden is greatest for patients with MASH is dependent on the age at which they contracted the disease: aged < 40: eighth decade (ages 70-79 years) and aged > 40: ninth decade (80-89 years). The model also found that the burden was higher for women owing to their longevity. Similarly at the population level, the greatest burden of MASH is expected to fall in the 70-79-year-old age group (6.46 million years of quality-adjusted life-expectancy [QALE]) and the 60-69-year-old age band (5.49 million years of QALE). Approximately 19.34 million years of QALE are lost in the US population (334 million) over their lifetime. The analysis shows that mortality is a greater burden than morbidity for MASH, and that owing to the insidious nature of the disease, burden is likely to be concentrated in the seventh to eighth decade of life (60-79-year-olds). The burden for females is higher than for males, without differential incidence, owing to women's longevity. The incidence of MASH is expected to rise owing to the increasing prevalence of obesity and diabetes in the population.