Additional Cost Research Articles

Inclisiran: the preclinical discovery and development of a novel therapy for the treatment of atherosclerosis

ABSTRACT Introduction Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of global morbidity and mortality. Lipid lowering therapy (LLT) constitutes the cornerstone of ASCVD prevention and treatment. However, several patients fail to achieve therapeutic goals due to low treatment adherence or limitations of standard-of-care (SoC) LLTs. Inclisiran represents a pivotal low-density lipoprotein cholesterol (LDL-C) lowering agent aiming to address current unmet needs in LLT. It is the first available small interfering RNA (siRNA) LLT, specifically targeting PCSK9 mRNA and leading to post-transcriptional gene silencing (PTGS) of the PCSK9 gene. Areas covered Promising phase III trials revealed an ~ 50% reduction in LDL-C levels with subcutaneous inclisiran administration on days 1 and 90, followed by semiannual booster shots. Coupled with inclisiran’s favorable safety profile, these findings led to its approval by both the EMA and FDA. Herein, the authors highlight the preclinical discovery and development of this agent and provide the reader with their expert perspectives. Expert opinion The evolution of gene-silencing treatments offers new perspectives in therapeutics. Inclisiran appears to have the potential to revolutionize ASCVD prevention and treatment, benefiting millions of patients. Ensuring widespread availability of Inclisiran, as well as managing additional healthcare costs that may arise, should be of paramount importance.

Cost-Effectiveness of Digital Mental Health Versus Usual Care During Humanitarian Crises in Lebanon: Pragmatic Randomized Trial

Background There is evidence from meta-analyses and systematic reviews that digital mental health interventions for depression, anxiety, and stress-related disorders tend to be cost-effective. However, no such evidence exists for guided digital mental health care in low and middle-income countries (LMICs) facing humanitarian crises, where the needs are highest. Step-by-Step (SbS), a digital mental health intervention for depression, anxiety, and stress-related disorders, proved to be effective for Lebanese citizens and war-affected Syrians residing in Lebanon. Assessing the cost-effectiveness of SbS is crucial because Lebanon’s overstretched health care system must prioritize cost-effective treatment options in the face of continuing humanitarian and economic crises. Objective This study aims to assess the cost-effectiveness of SbS in a randomized comparison with enhanced usual care (EUC). Methods The cost-effectiveness analysis was conducted alongside a pragmatic randomized controlled trial in 2 parallel groups comparing SbS (n=614) with EUC (n=635). The primary outcome was cost (in US $ for the reference year 2019) per treatment response of depressive symptoms, defined as >50% reduction of depressive symptoms measured using the Patient Health Questionnaire (PHQ). The secondary outcome was cost per remission of depressive symptoms, defined as a PHQ score <5 at last follow-up (5 months post baseline). The evaluation was conducted first from the health care perspective then from the societal perspective. Results Taking the health care perspective, SbS had an 80% probability to be regarded as cost-effective compared with EUC when there is a willingness to pay US $220 per additional treatment response or US $840 per additional remission. Taking the wider societal perspective, SbS had a >75% probability to be cost-saving while gaining response or remission. Conclusions To our knowledge, this study is the first cost-effectiveness analysis based on a large randomized controlled trial (n=1249) of a guided digital mental health intervention in an LMIC. From the principal findings, 2 implications flowed, from the (1) health care perspective and (2) wider societal perspective. First, our findings suggest that SbS is associated with greater health benefits, albeit for higher costs than EUC. It is up to decision makers in health care to decide if they find the balance between additional health gains and additional health care costs acceptable. Second, as seen from the wider societal perspective, there is a substantial likelihood that SbS is not costing more than EUC but is associated with cost-savings as SBS participants become more productive, thus offsetting their health care costs. This finding may suggest to policy makers that it is in the interest of both population health and the wider Lebanese economy to implement SbS on a wide scale. In brief, SbS may offer a scalable, potentially cost-saving response to humanitarian emergencies in an LMIC. Trial Registration ClinicalTrials.gov NCT03720769; https://clinicaltrials.gov/ct2/show/NCT03720769 International Registered Report Identifier (IRRID) RR2-10.2196/21585

Ionic liquid coating for charge mitigation of solar modules in space: Electron microscopy on insulating nanosphere lithography patterned surfaces

Surfaces of satellites and spacecrafts are exposed to high energy charged particles from the solar wind, especially during space weather events. This can lead to differential charging, which is a common reason for hardware degradation and sensor errors. Solutions like coatings are required to avoid excessive cost and weight. Mimicking the electron part of space-like environments in ultra-high vacuum (UHV) chambers can be achieved by using electrons emitted by a scanning electron microscope (SEM). As a performance test for the discharge capabilities we use the quality of electron microscopy images on otherwise insulating substrates such as glass, structured by nanosphere lithography and coated with an ionic liquid (IL). Additionally, the surface potential was measured by Kelvin Probe Force Spectroscopy. The IL film (BMP DCA) was applied ex situ and a thickness of 12.8 ($\pm$0.8)\,nm was determined by reflectometry and confirmed by dynamic atomic force microscopy. Such a film of ionic liquid would lead to additional mass of below 20\,mg and negligible additional material costs. The light absorption and influence of ionic liquid coatings on the current output of an actual solar cell were investigated. The results indicate, that these coatings are promising candidates for surface charge mitigation with a high potential for application

ESTIMATION OF GREEN BUILDING OVER CONVENTIONAL BUILDING

This report investigates the comparative costs and benefits of green building versus conventional building practices. By integrating five advanced techniques: Biophilic Design, Passive House Design Strategies, Digital Twin Technology, Net Zero Energy Techniques, and Water Harvesting System into the construction of a conventional building, we transformed it into a green building at an additional cost of approximately ₹6,72,420. The total cost for constructing the green building amounted to ₹24,23,876.78, inclusive of the base cost of a conventional building. The study outlines a comprehensive methodological approach, which includes creating theoretical models, conducting cost analyses using current market rates in India, and evaluating environmental impacts through carbon emissions calculations. The findings reveal that although the initial costs for green buildings are higher, they offer substantial long-term benefits, including reduced operational expenses, improved occupant health, and minimized environmental footprints. Green buildings are designed to maximize resource efficiency, enhance indoor air quality, and utilize renewable energy sources, resulting in significant energy savings and reduced carbon emissions. This investment in sustainable construction practices not only promotes environmental stewardship but also ensures economic viability through long-term savings and improved occupant well-being. The transition to green buildings is a crucial step towards addressing climate change and fostering sustainable development for future generations. This report underscores the importance of adopting green building techniques and demonstrates that the benefits far outweigh the initial financial outlay, making green buildings a worthwhile investment for a sustainable future.

Investigation of the Relationship Between Tumor Microenvironment and Prognostic Parameters in Invasive Breast Carcinomas of No Special Type: A Retrospective Analysis.

The tumor microenvironment is a heterogeneous and constantly changing territory that plays an active role in tumor formation and progression. It constantly interacts with tumor cells, plays an active role in tumor development, and even appears as a parameter of prognostic importance, and the importance of the tumor microenvironment in breast cancer has been emphasized by recent studies. In this study, we aimed to retrospectively evaluate the relationship between the tumor microenvironment and prognostic parameters in invasive breast carcinomas of no special type. A total of 271 cases diagnosed as invasive breast carcinoma of no special type from resection materials in our center between 2007 and 2015 were included in the study. Hematoxylin-eosin stained slides with a thickness of 4-5 micrometers were evaluated in terms of tumor infiltrating lymphocytes, peritumoral and intratumoral desmoplastic reaction, intratumoral and peritumoral tumor budding, stromal features, and tumor growth pattern. When parameters related to the tumor microenvironment were compared with other prognostic parameters, there was a significant relationship between TILs and tumor grade, size, stage, immunohistochemical subgroup and Ki-67 proliferation index. A significant relationship was detected between intratumoral stromal reaction and tumor grade, size, molecular subgroup and the Ki-67 proliferation index (p < 0.05). When stroma and other prognostic parameters were compared, tumors with desmoplastic stroma had higher grades and higher Ki-67 proliferation indexes, and they were observed more frequently in the triple negative molecular subgroup. We believe that including parameters related to tumor microenvironment in breast cancer reports, which hold a prognostic and predictive importance, will contribute to patient management. Considering the fact that these can be easily evaluated from routinely used hematoxylin-eosin stained slides, this does not cause additional costs or excessive time loss.

Procurement-network contributions to healthcare supply chain resilience: a case study from Canada

PurposeThis article investigates how the healthcare sector can reorganize its procurement network to better balance its resilience and cost-minimization objectives.Design/methodology/approachA single case study was conducted on the procurement of personal protective equipment (PPE) during the first COVID-19 pandemic wave in the Quebec public healthcare network. Interviews were conducted with stakeholders from the supply chain management (SCM) departments at eight public healthcare institutions.FindingsTwo major challenges in the early months of the pandemic impacted the development of resilience in the healthcare network. First, peripheral actors’ decisions, which orient procurement objectives, limited the deployment of resilience measures in the supply chain (SC). Second, SC resilience included hundreds of products other than PPE that are critical to the delivery of care. The article illustrates the challenges of SCR, which will inevitably be accompanied by additional costs when purchasing in the public healthcare sector is often focused on the lowest price.Originality/valueDrawing from the network perspective model, this article examines the actions of Quebec supply network stakeholders through the three phases of SCR: anticipation, response to disruption, and recovery. Finally, the article suggests that decision-makers remove the cost of resilience measures from the purchase price of products, in order to maintain these measures over the long term.

Should major trauma fractures be part of a fracture liaison service's remit: a cost-benefit estimate.

To compare the 3-year refracture rate following minimal trauma (MT) and non-minimal trauma (non-MT) injuries and evaluate the cost of extending fracture liaison service (FLS) operations to non-MT presentations. Patients aged 50, or above presenting to the John Hunter Hospital with a fracture in calendar year 2018 were identified through the Integrated Patient Management System (IPMS) of the Hunter New England Health Service's (HNEHS), and re-presentation to any HNEHS facility over the following 3years monitored. The refracture rate of MT and non-MT presentations was compared and analysed using Cox proportional hazards regression models. The cost of including non-MT patients was estimated through the use of a previously conducted micro-costing analysis. The operational fidelity of the FLS to the previous estimate was confirmed by comparing the 3-year refracture rate of MT presentations in the two studies. The 3-year refracture rate following a MT injury was 8% and after non-MT injury 4.5%. Extension of FLS activities to include non-MT patients in 2022 would have cost an additional $198,326 AUD with a notional loss/saving of $ - 26,625/ + 26,913 AUD through refracture risk reduction. No clinically available characteristic at presentation predictive of increased refracture risk was identified. The 3-year refracture after a non-MT injury is about half (57%) that of the refracture rate after a MT injury. Extending FLS activity to non-MT patients incurs a significant additional direct cost but remains cost neutral if notional savings gained through reduction in refracture risk are taken into account.

DFT Guided Design and Preparation of Quasi-Nanocrystalline Hf-La2O3 Cathode with Unprecedented Thermal Emission Performance.

With the guidance of density functional theory (DFT), a high-performance hafnium (Hf) cathode for an air/water vapor plasma torch is designed and the concepts and principles for high performance are elucidated. A quasi-nanocrystalline hexagonal close-packed (HCP) Hf-La2O3 cathode based on these design principles is successfully fabricated via a powder metallurgy route. Under identical voltage and temperature conditions, the thermal emission current density of this quasi-nanocrystalline Hf-La2O3 cathode is ≈20 times greater than that of conventional Hf cathodes. Additionally, its cathodic lifespan is significantly extended. Quasi-nanocrystalline Hf-La2O3 products are manufactured into cathode devices with standard dimensions. This fabrication process is straightforward, requires minimal doped oxides, and is cost-effective. Consequently, the approach offers substantial performance enhancements over traditional Hf melting methods without incurring significantly additional costs.

Comparison of the Coastal and Regional Ocean COmmunity model (CROCO) and NCAR-LES in non-hydrostatic simulations

Abstract. Advances in coastal modeling and computation provide the opportunity to examine non-hydrostatic and compressible fluid effects at very small scales, but the cost of these new capabilities and the accuracy of these models versus trusted non-hydrostatic codes has yet to be determined. Here the Coastal and Regional Ocean COmmunity model (CROCO, v1.2) and the National Center for Atmospheric Research large-eddy simulation (NCAR-LES) model are compared, with a focus on their simulation accuracy and computational efficiency. These models differ significantly in numerics and capabilities, so they are run on common classic problems of surface-forced, boundary-layer turbulence. In terms of accuracy, we compare turbulence statistics, including the effect of the explicit subgrid-scale (SGS) parameterization, the effect of the second (dilatational) viscosity, and the sensitivity to the speed of sound, which is used as part of the CROCO compressible turbulence formulation. To gauge how far CROCO is from the NCAR-LES, we first compare the NCAR-LES with two other non-hydrostatic Boussinesq approximation LES codes (PALM and Oceananigans), defining the notion and magnitude of accuracy for the LES and CROCO comparison. To judge efficiency of CROCO, strong and weak scaling simulation sets vary different problem sizes and workloads per processor, respectively. Additionally, the effects of 2D decomposition of CROCO and NCAR-LES and supercomputer settings are tested. In summary, the accuracy comparison between CROCO and the NCAR-LES is similar to the NCAR-LES compared to other LES codes. However, the additional capabilities of CROCO (e.g., nesting, non-uniform grid, and realism of ocean configuration in general) and its weakly compressible formulation come with roughly an order of magnitude of additional costs, despite efforts to reduce them by adjusting the second viscosity and speed of sound as far as accuracy allows. However, a new variant of the non-hydrostatic CROCO formulation is currently undergoing prototype testing and should enable faster simulations by releasing the stability constrain by the free surface. Overall, when the additional features of CROCO are needed (nesting, complex topography, etc.) additional costs are justified, while in idealized settings (a rectangular domain with periodic boundary conditions) the NCAR-LES is faster in arriving at nearly the same result.

Cost-Effectiveness of Test-and-Treat Strategies to Reduce the Antibiotic Prescription Rate for Acute Febrile Illness in Primary Healthcare Clinics in Africa.

Inappropriate antibiotic use increases selective pressure, contributing to antimicrobial resistance. Point-of-care rapid diagnostic tests (RDTs) would be instrumental to better target antibiotic prescriptions, but widespread implementation of diagnostics for improved management of febrile illnesses is limited. Our study aims to contribute to evidence-based guidance to inform policymakers on investment decisions regarding interventions that foster more appropriate antibiotic prescriptions, as well as to address the evidence gap on the potential clinical and economic impact of RDTs on antibiotic prescription. A country-based cost-effectiveness model was developed for Burkina Faso, Ghana and Uganda. The decision tree model simulated seven test strategies for patients with febrile illness to assess the effect of different RDT combinations on antibiotic prescription rate (APR), costs and clinical outcomes. The incremental cost-effectiveness ratio (ICER) was expressed as the incremental cost per percentage point (ppt) reduction in APR. For Burkina Faso and Uganda, testing all patients with a malaria RDT was dominant compared to standard-of-care (SoC) (which included malaria testing). Expanding the test panel with a C-reactive protein (CRP) test resulted in an ICER of $0.03 and $0.08 per ppt reduction in APR for Burkina Faso and Uganda, respectively. For Ghana, the pairwise comparison with SoC-including malaria and complete blood count testing-indicates that both testing with malaria RDT only and malaria RDT + CRP are dominant. The use of RDTs for patients with febrile illness could effectively reduce APR at minimal additional costs, provided diagnostic algorithms are adhered to. Complementing SoC with CRP testing may increase clinicians' confidence in prescribing decisions and is a favourable strategy.

Analysis of the parasitological situation regarding eimeriosis in cattle in the Russian Federation

The purpose of the study is to review the spread of bovine eimeriosis in the territory of the Russian Federation. Objectives of the study: to analyze the epizootic situation of bovine eimeriosis in the territory of the Russian Federation. Bovine coccidiosis is widespread in many regions of Russia and in other countries of the world. The pathogens are more than 10 species of eimeria, which have a specific localization in the body of animals, as well as morphological differences from each other. Three species (E. zuernii, E. bovis and E. alabamensis) are characterized by the highest pathogenicity and are most often associated with the clinical manifestation of the disease. Mostly young animals aged from 2 weeks to 1 year are ill, and adult animals have an asymptomatic form of invasion. In many animals, eimeria causes dangerous diseases, accompanied by a decrease in productivity, the birth of weak offspring, often the death of young animals, and additional feed costs per unit of production. In livestock complexes, the incidence of calves with eimeriosis is 10–100%, and mortality is 25–60%. The maximum infection of calves and adult animals is observed in the spring and autumn periods, and in some regions in the autumn-winter period. It was found that with an increase in the density of calves in the machine, their infection with eimeria increases significantly. The invasion of calves was minimal when kept in individual machines. Given that parasites have a complex developmental biology, one of the most importantmeasures in the complex of measures ensuring the prevention and elimination of animal diseases with coccidiosis is currently still pharmacotherapy and prevention, contributing not only to the liberation of animals from parasites, but also to prevent the dispersion of the invasive origin in the environment and to prevent the threat of new infection.

Ecology for the rich? Class aspects of the green transition and the threat of right-wing populism as a reaction to its costs in Poland

This article sheds light on the class determinants of ecological attitudes and, at the same time, tries to emphasize the general importance of class differentiation for the implementation of sustainable development policies. This is particularly important in Eastern European countries where, for financial reasons, a green transition raises concerns among social groups that may feel threatened by additional socioeconomic costs. Using empirical data collected in Poland, we point out that the challenges, implementation, and social costs of a green transition can be used by populist and nationalist right-wing politicians. At the same time, right-wing populists depict ecological activists as a threat to the interests of “ordinary people” and identify them with the liberal metropolitan elites, detached from the worries of people with lower incomes and residents of traditionalist provinces. In the current conditions, the fear of increases in energy and fuel prices may be another source of support for an anti-ecological right-wing agenda against the “global pressure” of the liberal establishment. This narrative may be particularly attractive in peripheral and semi-peripheral countries in Europe and around the world as it refers not only to ideological arguments but also to the economic interests of “ordinary people.”

Developing a Cost-Effective Surgical Scheduling System Applying Lean Thinking and Toyota's Methods for Surgery-Related Big Data for Improved Data Use in Hospitals: User-Centered Design Approach.

Surgical scheduling is pivotal in managing daily surgical sequences, impacting patient experience and hospital resources significantly. With operating rooms costing approximately US $36 per minute, efficient scheduling is vital. However, global practices in surgical scheduling vary, largely due to challenges in predicting individual surgeon times for diverse patient conditions. Inspired by the Toyota Production System's efficiency in addressing similar logistical challenges, we applied its principles as detailed in the book "Lean Thinking" by Womack and Jones, which identifies processes that do not meet customer needs as wasteful. This insight is critical in health care, where waste can compromise patient safety and medical quality. This study aims to use lean thinking and Toyota methods to develop a more efficient surgical scheduling system that better aligns with user needs without additional financial burdens. We implemented the 5 principles of the Toyota system: specifying value, identifying the value stream, enabling flow, establishing pull, and pursuing perfection. Value was defined in terms of meeting the customer's needs, which in this context involved developing a responsive and efficient scheduling system. Our approach included 2 subsystems: one handling presurgery patient data and another for intraoperative and postoperative data. We identified inefficiencies in the presurgery data subsystem and responded by creating a comprehensive value stream map of the surgical process. We developed 2 Excel (Microsoft Corporation) macros using Visual Basic for Applications. The first calculated average surgery times from intra- or postoperative historic data, while the second estimated surgery durations and generated concise, visually engaging scheduling reports from presurgery data. We assessed the effectiveness of the new system by comparing task completion times and user satisfaction between the old and new systems. The implementation of the revised scheduling system significantly reduced the overall scheduling time from 301 seconds to 261 seconds (P=.02), with significant time reductions in the revised process from 99 seconds to 62 seconds (P<.001). Despite these improvements, approximately 21% of nurses preferred the older system for its familiarity. The new system protects patient data privacy and streamlines schedule dissemination through a secure LINE group (LY Corp), ensuring seamless flow. The design of the system allows for real-time updates and has been effectively monitoring surgical durations daily for over 3 years. The "pull" principle was demonstrated when an unplanned software issue prompted immediate, user-led troubleshooting, enhancing system reliability. Continuous improvement efforts are ongoing, except for the preoperative patient confirmation step, which requires further enhancement to ensure optimal patient safety. Lean principles and Toyota's methods, combined with computer programming, can revitalize surgical scheduling processes. They offer effective solutions for surgical scheduling challenges and enable the creation of a novel surgical scheduling system without incurring additional costs.

Preconditioning Strategies for Truncated Newton Full-waveform Inversion

ABSTRACT. Truncated Newton full waveform inversion is an attractive alternative to conventional gradient-based optimization algorithms. This method accounts for the Hessian within the inversion; however, it is implemented in a "Hessian-free" fashion, without explicit calculation or storage of the Hessian matrix. At each iteration, we obtain the search direction through a conjugate-gradient (CG) solution of the Newton linear system, which requires only evaluations of Hessian-vector products. Due to the additional cost associated with inner CG iterations, it is indispensable to apply a preconditioning strategy on the CG algorithm to improve its convergence, reducing the number of CG iterations. In this work, we study two preconditioned CG schemes. We propose a scheme based on model reparameterization that adopts a preconditioner operator that combines smoothness and the illumination compensation effect of the pseudo-Hessian. We also investigate a more conventional preconditioning scheme that uses only the pseudo-Hessian preconditioner. The numerical experiments show that preconditioning using model reparameterization, which combines pseudo-Hessian compensation with smoothing, outperforms the more conventional preconditioning scheme that exclusively uses the pseudo-Hessian operator.

Challenges Regarding the Value of Routine Perioperative Transesophageal Echocardiography in Mitral Valve Surgery

Background and Objectives: Transesophageal echocardiography (TEE) is considered an indispensable tool for perioperative evaluation in mitral valve (MV) surgery. TEE is routinely performed by anesthesiologists competent in TEE; however, in certain situations, the expertise of a senior cardiologist specializing in TEE is required, which incurs additional costs. The purpose of this study is to determine the indications for specialized perioperative TEE based on its utility and the correlation between intraoperative TEE diagnoses and surgical findings, compared with routine TEE performed by an anesthesiologist. Materials and Methods: We conducted a three-year prospective study involving 499 patients with MV disease undergoing cardiac surgery. Patients underwent intraoperative and early postoperative TEE and at least one other perioperative echocardiographic evaluation. A computer application was dedicated to calculating the utility of each type of specialized TEE indication depending on the type of MV disease and surgical intervention. Results: The indications for performing specialized perioperative TEE identified in our study can be categorized into three groups: standard, relative, and uncertain. Standard indications for specialized intraoperative TEE included establishing the mechanism and severity of MR (mitral regurgitation), guiding MV valvuloplasty, diagnosing associated valvular lesions post MVR (mitral valve replacement), routine evaluations in triple-valve replacements, and identifying the causes of acute, intraoperative, life-threatening hemodynamic dysfunction. Early postoperative specialized TEE in the intensive care unit (ICU) is indicated for the suspicion of pericardial or pleural effusions, establishing the etiology of acute hemodynamic dysfunction, and assessing the severity of residual MR post valvuloplasty. Conclusions: Perioperative TEE in MV surgery can generally be performed by a trained anesthesiologist for standard measurements and evaluations. In certain cases, however, a specialized TEE examination by a trained senior cardiologist is necessary, as it is indirectly associated with a decrease in postoperative complications and early postoperative mortality rates, as well as an improvement in immediate and long-term prognoses. Also, for standard indications, the correlation between surgical and TEE diagnoses was superior when specialized TEE was used.

A shortest‐path‐aided fast‐sweeping method to improve the accuracy of traveltime calculation in vertically transverse isotropic media

AbstractThe high accuracy and efficiency of traveltime calculation are critical in seismic tomography, migration, static corrections, source locations and anisotropic parameter estimation. The fast‐sweeping method is an efficient upwind finite‐difference approach for solving the eikonal equation. However, the fast‐sweeping method is accurate only along the axis directions. In two‐dimensional or higher dimensional cases, the accuracy is severely decreased in the diagonal directions due to the numerical errors in these directions. These similar numerical errors also arose in higher order fast‐sweeping method and anisotropic fast‐sweeping method. To improve the accuracy of traveltime calculation in two‐dimensional or higher dimensional space, a shortest‐path‐aided fast‐sweeping method is proposed. The shortest‐path‐aided solution is embedded into the sweeping process of the standard fast‐sweeping method to improve the traveltime accuracy in the diagonal directions. Shortest‐path‐aided fast‐sweeping method is very easy to implement nearly without additional computational cost and memory consumption. Furthermore, this method is easy to extend from two‐dimensional to higher dimensional, from low‐order to higher‐order and from isotropic to anisotropic cases.

Periprosthetic Joint Infection After Total Knee Arthroplasty With or Without Antibiotic Bone Cement

Despite increased use of antibiotic-loaded bone cement (ALBC) in joint arthroplasty over recent decades, current evidence for prophylactic use of ALBC to reduce risk of periprosthetic joint infection (PJI) is insufficient. To compare the rate of revision attributed to PJI following primary total knee arthroplasty (TKA) using ALBC vs plain bone cement. This international cohort study used data from 14 national or regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, New Zealand, Norway, Romania, Sweden, Switzerland, the Netherlands, the UK, and the US. The study included primary TKAs for osteoarthritis registered from January 1, 2010, to December 31, 2020, and followed-up until December 31, 2021. Data analysis was performed from April to September 2023. Primary TKA with ALBC vs plain bone cement. The primary outcome was risk of 1-year revision for PJI. Using a distributed data network analysis method, data were harmonized, and a cumulative revision rate was calculated (1 - Kaplan-Meier), and Cox regression analyses were performed within the 10 registries using both cement types. A meta-analysis was then performed to combine all aggregated data and evaluate the risk of 1-year revision for PJI and all causes. Among 2 168 924 TKAs included, 93% were performed with ALBC. Most TKAs were performed in female patients (59.5%) and patients aged 65 to 74 years (39.9%), fully cemented (92.2%), and in the 2015 to 2020 period (62.5%). All participating registries reported a cumulative 1-year revision rate for PJI of less than 1% following primary TKA with ALBC (range, 0.21%-0.80%) and with plain bone cement (range, 0.23%-0.70%). The meta-analyses based on adjusted Cox regression for 1 917 190 TKAs showed no statistically significant difference at 1 year in risk of revision for PJI (hazard rate ratio, 1.16; 95% CI, 0.89-1.52) or for all causes (hazard rate ratio, 1.12; 95% CI, 0.89-1.40) among TKAs performed with ALBC vs plain bone cement. In this study, the risk of revision for PJI was similar between ALBC and plain bone cement following primary TKA. Any additional costs of ALBC and its relative value in reducing revision risk should be considered in the context of the overall health care delivery system.

Cost-effectiveness analysis of atezolizumab plus bevacizumab compared with sorafenib as first-line treatment in advanced hepatocellular carcinoma in Singapore

ABSTRACT Objectives This study aims to explore the cost-effectiveness of atezolizumab plus bevacizumab against sorafenib for first-line treatment of locally advanced or metastatic hepatocellular carcinoma (HCC) in Singapore. Methods A partitioned survival model was developed from a healthcare system perspective, with a 10-year lifetime horizon. Clinical inputs and utilities were obtained from the IMbrave150 trial. Healthcare resource use costs were obtained from published local sources; drug costs reflected the most recent public hospital selling prices. Outcomes included life years, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses were performed to assess the model’s robustness. Results Atezolizumab plus bevacizumab offered an additional 1.42 life years and 1.09 QALYs, with an additional cost of S$111,847; the ICER was S$102,988/QALY. The World Health Organization considers interventions with ICERs <1 gross domestic product (GDP)/capita to be highly cost-effective. At a willingness-to-pay (WTP) threshold of S$114,165/QALY (Singapore’s 2022 GDP/capita), atezolizumab plus bevacizumab is cost-effective compared with sorafenib. The ICER was most sensitive to variations in utilities, but all parameter variations had no significant impact on the model outcomes. Conclusion At a WTP threshold of Singapore’s GDP/capita, atezolizumab plus bevacizumab is cost-effective compared with sorafenib.

A temporal enhanced semi-supervised training framework for needle segmentation in 3D ultrasound images

Objective. Automated biopsy needle segmentation in 3D ultrasound images can be used for biopsy navigation, but it is quite challenging due to the low ultrasound image resolution and interference similar to the needle appearance. For 3D medical image segmentation, such deep learning networks as convolutional neural network and transformer have been investigated. However, these segmentation methods require numerous labeled data for training, have difficulty in meeting the real-time segmentation requirement and involve high memory consumption. Approach. In this paper, we have proposed the temporal information-based semi-supervised training framework for fast and accurate needle segmentation. Firstly, a novel circle transformer module based on the static and dynamic features has been designed after the encoders for extracting and fusing the temporal information. Then, the consistency constraints of the outputs before and after combining temporal information are proposed to provide the semi-supervision for the unlabeled volume. Finally, the model is trained using the loss function which combines the cross-entropy and Dice similarity coefficient (DSC) based segmentation loss with mean square error based consistency loss. The trained model with the single ultrasound volume input is applied to realize the needle segmentation in ultrasound volume. Main results. Experimental results on three needle ultrasound datasets acquired during the beagle biopsy show that our approach is superior to the most competitive mainstream temporal segmentation model and semi-supervised method by providing higher DSC (77.1% versus 76.5%), smaller needle tip position (1.28 mm versus 1.87 mm) and length (1.78 mm versus 2.19 mm) errors on the kidney dataset as well as DSC (78.5% versus 76.9%), needle tip position (0.86 mm versus 1.12 mm) and length (1.01 mm versus 1.26 mm) errors on the prostate dataset. Significance. The proposed method can significantly enhance needle segmentation accuracy by training with sequential images at no additional cost. This enhancement may further improve the effectiveness of biopsy navigation systems.

Burden of Disease Study of Patients with Neovascular Age-Related Macular Degeneration in Spain.

Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that causes severe and irreversible vision loss. The disease can therefore have a significant impact on the life of patients' and their families. The aim of this study was to evaluate the socio-economic burden of nAMD in Spain. The annual cost per patient with nAMD was estimated for the first, second, and third year (or beyond) of treatment since diagnosis. Several cost categories were considered including direct healthcare costs (DHC), direct non-healthcare costs (DNHC), labor productivity losses (LPL), and intangible costs (IC) related to loss of quality of life. The average annual cost per patient was estimated by assigning a unit price or financial proxy to the resources consumed per patient. Reference year of costs was 2021. The mean annual cost of nAMD was estimated at €17,265, €15,403, and €14,465 per patient in the first, second, and third year of treatment after diagnosis. There was an additional one-off cost of €744 associated with the diagnosis of nAMD. DHC accounted for most of the total annual cost per patient independent of the year of treatment since diagnosis (48% in year1; 42% in year2; 39% in year3). Similarly, DNHC had an important contribution to the total costs (32% in year1; 35% in year2; 37% in year3), followed by IC (20% in year1; 23% in year2; 24% in year3), while the contribution of patients' LPL was minimal. This study estimated a high economic burden associated with nAMD for patients and their families, the healthcare system, and society at large. There is a need to improve the management of these patients to reduce the impact of nAMD disease progression.