Subgraph Isomorphic Decision Tree to Predict Radical Thermochemistry with Bounded Uncertainty Estimation.

Detailed chemical kinetic models offer valuable mechanistic insights into industrial applications. Automatic generation of reliable kinetic models requires fast and accurate radical thermochemistry estimation. Kineticists often prefer hydrogen bond increment (HBI) corrections from a closed-shell molecule to the corresponding radical for their interpretability, physical meaning, and facilitation of error cancellation as a relative quantity. Tree estimators, used due to limited data, currently rely on expert knowledge and manual construction, posing challenges in maintenance and improvement. In this work, we extend the subgraph isomorphic decision tree (SIDT) algorithm originally developed for rate estimation to estimate HBI corrections. We introduce a physics-aware splitting criterion, explore a bounded weighted uncertainty estimation method, and evaluate aleatoric uncertainty-based and model variance reduction-based prepruning methods. Moreover, we compile a data set of thermochemical parameters for 2210 radicals involving C, O, N, and H based on quantum chemical calculations from recently published works. We leverage the collected data set to train the SIDT model. Compared to existing empirical tree estimators, the SIDT model (1) offers an automatic approach to generating and extending the tree estimator for thermochemistry, (2) has better accuracy and R2, (3) provides significantly more realistic uncertainty estimates, and (4) has a tree structure much more advantageous in descent speed. Overall, the SIDT estimator marks a great leap in kinetic modeling, offering more precise, reliable, and scalable predictions for radical thermochemistry.

An Economic Analysis of Transjugular Intrahepatic Portosystemic Covered Stent Shunt for Variceal Bleeding and Refractory Ascites in a Spanish Setting.

INTRODUCTION: The primary aim is to estimate the cost-effectiveness of transjugular intrahepatic portosystemic stent shunt (TIPSS) in two indications from a Spanish perspective. Firstly, as pre-emptive treatment for patients with acute variceal bleeding (indication 1) compared with endoscopic band ligation plus drug therapy. Secondly, to treat refractory ascites (indication 2) compared with large volume paracentesis. METHODS: A two-state (alive and dead) Markov model was developed to capture the costs and health impact for the two indications over a 2-year time horizon with monthly cycles. In the alive state, patients could experience adverse event(s), associated with costs and disutility, such as recurrent variceal bleeding, ascites, and hepatic encephalopathy. Discount rates of 3% for utilities and costs and a cost-effectiveness threshold of €25,000 per QALY were applied. RESULTS: In the base case analysis, TIPSS was estimated to be cost-effective as a pre-emptive treatment for indication 1 (incremental cost and QALYs of - €230 and 0.211, respectively). TIPSS also remained cost-effective (€16,819/QALY) in a conservative scenario analysis, conducted with an alternate source for clinical parameters. The key drivers of the outcomes were survival for the comparator arm, mean band ligation outpatient procedures, and TIPSS treatment costs. TIPSS was estimated to dominate the comparator for indication 2 (incremental cost and QALYs of - €25,687 and 0.531, respectively). The key drivers of the outcomes were monthly paracentesis sessions and cost per inpatient stay for those undergoing paracentesis. CONCLUSIONS: TIPSS is likely to be a cost-effective and a cost-saving treatment in patients with cirrhosis in indications 1 and 2, compared with standard treatments. The analyses estimate clinical benefits along with reduced healthcare costs from avoided downstream resource consumption.

Lymph node assessment technique matters in radical cystectomy for bladder cancer.

BACKGROUND: For patients undergoing radical cystectomy with pelvic lymph node dissection for urothelial cancer, a lymph node count of at least 16 is associated with improved cancer-specific and overall survival. Lymph node yield is presumed to relate directly to extent of dissection and surgical quality, however limited studies have reviewed the impact of the pathological assessment process of lymph nodes on lymph node yield. METHOD: A retrospective assessment of 139 patients who had radical cystectomy for urothelial cancer between March 2015 and July 2021 from Fiona Stanley Hospital (Perth, Australia) by a single surgeon was assessed. A change in pathological assessment process from assessment of only palpable lymph nodes to microscopic assessment of the entire submitted specimens occurred in August 2018. Patients were divided into two groups accordingly and other relevant demographic and pathological data was recorded. The impact of pathological processing technique on lymph node yield was assessed using the Student T test and logistical regression was used to assess the impact of other demographic variables. RESULTS: The mean lymph node yield was 16.2 nodes (IQR 12-23) in 54 patients in the pre-process change group compared to 22.4 nodes (IQR 15-28.4) in 85 patients in the post-process change group (P < 0.0001). 53.7% had 16 or more nodes in the pre-process change group compared to 71.3% in the post-process change group (P = 0.04). Age, BMI, and gender were not significant predictors of lymph node yield. CONCLUSION: The current study demonstrates that the microscopic assessment of all lymph node tissue detects significantly more lymph nodes than only examining palpably abnormal tissue. Pathologic assessment protocols should be standardized to this technique to ensure the utility of lymph node yield as a quality metric.

Economic significance of biofilms: a multidisciplinary and cross-sectoral challenge.

The increasing awareness of the significance of microbial biofilms across different sectors is continuously revealing new areas of opportunity in the development of innovative technologies in translational research, which can address their detrimental effects, as well as exploit their benefits. Due to the extent of sectors affected by microbial biofilms, capturing their real financial impact has been difficult. This perspective highlights this impact globally, based on figures identified in a recent in-depth market analysis commissioned by the UK's National Biofilms Innovation Centre (NBIC). The outputs from this analysis and the workshops organised by NBIC on its research strategic themes have revealed the breath of opportunities for translational research in microbial biofilms. However, there are still many outstanding scientific and technological challenges which must be addressed in order to catalyse these opportunities. This perspective discusses some of these challenges.

An Integrated Assessment of Emissions, Air Quality, and Public Health Impacts of China's Transition to Electric Vehicles.

Electric vehicles (EVs) are a promising pathway to providing cleaner personal mobility. China provides substantial supports to increase EV market share. This study provides an extensive analysis of the currently unclear environmental and health benefits of these incentives at the provincial level. EVs in China have modest cradle-to-gate CO2 benefits (on average 29%) compared to conventional internal combustion engine vehicles (ICEVs), but have similar carbon emissions relative to hybrid electric vehicles. Well-to-wheel air pollutant emissions assessment shows that emissions associated with ICEVs are mainly from gasoline production, not the tailpipe, suggesting tighter emissions controls on refineries are needed to combat air pollution problems effectively. By integrating a vehicle fleet model into policy scenario analysis, we quantify the policy impacts associated with the passenger vehicles in the major Chinese provinces: broader EV penetration, especially combined with cleaner power generation, could deliver greater air quality and health benefits, but not necessarily significant climate change mitigation. The total value to society of the climate and mortality benefits in 2030 is found to be comparable to a prior estimate of the EV policy's economic costs.

An Economic Analysis of the Impact of Homecare Drug Administration for Biologic Interventions Available for Plaque Psoriasis in the UK.

INTRODUCTION: In the UK, biologic interventions for plaque psoriasis can either be administered in a hospital setting or following delivery to a patient's home. To date, limited research has been undertaken on how the administration route affects the overall treatment costs and the implications for this on UK clinical practice. The objective was to explore the cost implications of different administration routes for plaque psoriasis biologic interventions in the UK. METHODS: A simple economic model was developed to estimate and compare the total cost of drug administration over 2 years for all biologic interventions that have been approved by the National Institute of Health and Care Excellence for use in patients with moderate-to-severe plaque psoriasis. Administration costs were estimated for two different scenarios: administration in a hospital setting or following home delivery [paid for by the National Health Service (NHS)]. RESULTS: Costs of home delivery and administration in hospital over a 2-year time horizon varied substantially based on the choice of intervention. For home delivery, the lowest cost of £693 occurred with risankizumab, tildrakizumab and ustekinumab, while the highest cost of £3445 occurred with adalimumab, brodalumab, certolizumab and etanercept. For the scenario in which the interventions were administered in a hospital setting the costs ranged from £4224 for ustekinumab to £7463 for brodalumab. CONCLUSION: These results indicate that drug administration costs are meaningful and should be given greater consideration in the selection process of treatments for plaque psoriasis. Additionally, the NHS could save money by paying for drugs to be delivered to a patient's home, rather than administering them in a hospital setting.

An Economic Analysis of the Impact of Homecare Drug Administration for Biologic Interventions Available for Plaque Psoriasis in the UK.

INTRODUCTION: In the UK, biologic interventions for plaque psoriasis can either be administered in a hospital setting or following delivery to a patient's home. To date, limited research has been undertaken on how the administration route affects the overall treatment costs and the implications for this on UK clinical practice. The objective was to explore the cost implications of different administration routes for plaque psoriasis biologic interventions in the UK. METHODS: A simple economic model was developed to estimate and compare the total cost of drug administration over 2 years for all biologic interventions that have been approved by the National Institute of Health and Care Excellence for use in patients with moderate-to-severe plaque psoriasis. Administration costs were estimated for two different scenarios: administration in a hospital setting or following home delivery [paid for by the National Health Service (NHS)]. RESULTS: Costs of home delivery and administration in hospital over a 2-year time horizon varied substantially based on the choice of intervention. For home delivery, the lowest cost of £693 occurred with risankizumab, tildrakizumab and ustekinumab, while the highest cost of £3445 occurred with adalimumab, brodalumab, certolizumab and etanercept. For the scenario in which the interventions were administered in a hospital setting the costs ranged from £4224 for ustekinumab to £7463 for brodalumab. CONCLUSION: These results indicate that drug administration costs are meaningful and should be given greater consideration in the selection process of treatments for plaque psoriasis. Additionally, the NHS could save money by paying for drugs to be delivered to a patient's home, rather than administering them in a hospital setting.

Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study.

BACKGROUND: COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years. METHODS: Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic. FINDINGS: In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV and tuberculosis epidemics. INTERPRETATION: Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development, and Medical Research Council.

Recent Developments in Health Economic Modelling of Cancer Therapies.

Arguably, the most common structure currently adopted for oncology modelling is the three-state partitioned survival model with the following states: stable disease, post-progression and dead. This design can, therefore, be adopted to capture the progressive nature of cancer. This chapter outlines the three-state model approach as well as introducing several other key aspects of economic modelling in oncology.

Cost-effectiveness of SQ® HDM SLIT-tablet in addition to pharmacotherapy for the treatment of house dust mite allergic rhinitis in Germany.

BACKGROUND: Allergic rhinitis is a global health problem that burdens society due to associated health care costs and its impact on health. Standardized quality (SQ®) house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet is a sublingually administered allergy immunotherapy tablet for patients with persistent moderate to severe HDM allergic rhinitis despite use of allergy pharmacotherapy. OBJECTIVE: To assess the cost-effectiveness of SQ HDM SLIT-tablet in Germany for patients suffering from HDM allergic rhinitis. METHODS: A pharmacoeconomic analysis, based on data collected in a double-blinded, phase III randomized placebo-controlled trial (n=992), was undertaken to compare SQ HDM SLIT-tablet in addition to allergy pharmacotherapy to placebo plus allergy pharmacotherapy. Quality-adjusted life year (QALY) scores and health care resource use data recorded in the trial were applied to each treatment group and extrapolated over a nine-year time horizon. A series of scenarios were used to investigate the impact of changes on long-term patient health for both treatment groups, which was measured by annual changes in QALY scores. Deterministic and probabilistic sensitivity analyses were also performed. RESULTS: In the base case analysis, compared with allergy pharmacotherapy, SQ HDM SLIT-tablet led to a QALY gain of 0.31 at an incremental cost of €2,276 over the nine-year time horizon, equating to an incremental cost-effectiveness ratio of €7,519. The treatment was cost-effective for all scenarios analyzed; however, results were sensitive to changes in individual parameter values during the deterministic sensitivity analysis. CONCLUSION: SQ HDM SLIT-tablet in addition to pharmacotherapy is cost-effective compared with allergy pharmacotherapy plus placebo for the treatment of persistent moderate to severe HDM allergic rhinitis that is not well controlled by allergy pharmacotherapy.

Review of Economic Submissions to NICE Medical Technologies Evaluation Programme.

The economic evaluation of medical devices is increasingly used to inform decision making on adopting new or novel technologies; however, challenges are inevitable due to the unique characteristics of devices. Cost-consequence analyses are recommended and employed by the English National Institute for Health and Care Excellence (NICE) Medical Technologies Evaluation Programme (MTEP) to help address these challenges. The aim of this work was to review the critiques raised for previous MTEP submissions and explore if there were common problems across submissions. We reviewed a sample of 12 economic submissions to MTEP representing 50 % of 24 sets of guidance issued to July 2015. For each submission, we reviewed the External Assessment Centre's (EAC) report and the guidance document produced by NICE. We identified the main problems raised by the EAC's assessments and the committee's considerations for each submission, and explored strategies for improvement. We found that the identification and measurement of costs and consequences are the main shortcomings within economic submissions to MTEP. Together, these shortcomings accounted for 42 % of criticisms by the EACs among the reviewed submissions. In certain circumstances problems with these shortcomings may be unavoidable, for example, if there is a limited evidence base for the device being appraised. Nevertheless, strategies can often be adopted to improve submissions, including the use of more appropriate time horizons, whilst cost and resource use information should be taken, where possible, from nationally representative sources.

Cost-Effectiveness Analysis of d-Nav for People with Diabetes at High Risk of Neuropathic Foot Ulcers.

INTRODUCTION: The objective of this study was to assess the cost-effectiveness of the d-Nav Insulin Guidance Service (Hygieia Inc.), a system designed to improve glycemic control via the use of insulin titration, in people with diabetes at risk of developing neuropathic foot ulcers. METHODS: A Markov model containing four health states (no ulcer, uninfected ulcer, infected ulcer, and amputation) was developed to compare d-Nav with current National Health Service standard care. Patient movement between the health states was governed by event rates taken from the wider literature. Both the healing rate for uninfected ulcers and the rate of recurrence for uninfected ulcers were directly influenced by the patient's glycated hemoglobin (HbA1c). Separate mean HbA1c values were assigned to treatment and control patients and taken from a single-arm study that examined the effect of d-Nav on the outcomes of 122 patients, with HbA1c for control patients based on values recorded in the 12-month period prior to the study and HbA1c for d-Nav based on values recorded during the trial. Weekly cycles were applied, and patient resource use and quality-adjusted life years (QALYs) were estimated over a 3-year time horizon. Univariate sensitivity analysis was undertaken. RESULTS: In the base case, d-Nav was cost-saving and produced more QALYs than standard care, with a total net monetary benefit value of £1459 per patient. Univariate analysis indicated that the model results are relatively robust to variations in underlying parameters, with patient HbA1c having the most significant impact on outcomes. CONCLUSION: Interventions that aim to improve glycemic control, such as d-Nav, appear to be a cost-effective use of healthcare resources when targeted at those with poor glycemic control at high risk of developing foot ulcers. FUNDING: Hygieia Inc.

A systematic review of approaches for calculating the cost of medication errors.

INTRODUCTION: Although medication errors may cause significant morbidity and mortality, the true cost of avoidable harm from such errors is unclear. While studies describe different methods for calculating a financial cost from an error, there remains variability in the way calculations are conducted depending on the clinical context. This review aimed to investigate the range of approaches for calculating medication error costs across healthcare settings. METHODS: A systematic review was carried out with a duplicate data extraction approach and mixed methods data synthesis. Medline, Embase and Web of Science were searched for studies published between 1993 and 2015. Studies that explicitly described a method for calculating medication error cost were included. The variables used for the calculations and a description of the approach for calculating errors were reported. RESULTS: 21 studies were included in the final review. There was wide variation in the way calculations were undertaken, with some calculations using a single variable only and others using several variables in a multistep approach. Few calculations included indirect costs, such as loss of earnings for the patient, and only one calculation considered opportunity cost. The majority of studies presented direct medication error costs whereas others approximated error costs from the savings made following an intervention. CONCLUSIONS: There are a wide range of methods used for calculating the cost of medication errors. The diversity arises from the number of variables used in calculations, the perspective from which the calculation is conducted from, and the degree of economic rigour applied by researchers.

Economic and environmental benefits of higher-octane gasoline.

We quantify the economic and environmental benefits of designing U.S. light-duty vehicles (LDVs) to attain higher fuel economy by utilizing higher octane (98 RON) gasoline. We use engine simulations, a review of experimental data, and drive cycle simulations to estimate the reduction in fuel consumption associated with using higher-RON gasoline in individual vehicles. Lifecycle CO2 emissions and economic impacts for the U.S. LDV fleet are estimated based on a linear-programming refinery model, a historically calibrated fleet model, and a well-to-wheels emissions analysis. We find that greater use of high-RON gasoline in appropriately tuned vehicles could reduce annual gasoline consumption in the U.S. by 3.0-4.4%. Accounting for the increase in refinery emissions from production of additional high-RON gasoline, net CO2 emissions are reduced by 19-35 Mt/y in 2040 (2.5-4.7% of total direct LDV CO2 emissions). For the strategies studied, the annual direct economic benefit is estimated to be $0.4-6.4 billion in 2040, and the annual net societal benefit including the social cost of carbon is estimated to be $1.7-8.8 billion in 2040. Adoption of a RON standard in the U.S. in place of the current antiknock index (AKI) may enable refineries to produce larger quantities of high-RON gasoline.

Cost minimization analysis of preoperative erythropoietin vs autologous and allogeneic blood donation in total joint arthroplasty.

Autologous blood donation and erythropoietin (EPO) have been shown to be effective in reducing allogeneic blood transfusion, but the cost-effectiveness of these interventions remains unclear. A cost minimization analysis was performed, comparing the total costs of allogeneic blood transfusion strategy and autologous and allogeneic blood transfusion strategy for 161 primary total hip arthroplasty (THA) and 195 total knee arthroplasty (TKA) patients. An EPO cost minimization model was constructed using a previously published algorithm for blood management after total joint arthroplasty. The least costly strategy was autologous blood donation in combination with allogeneic blood for THA and TKA patients at $856 and $892 per patient, respectively. The most costly strategy was allogeneic only at $1769 and $1352 per THA and TKA patient, respectively. The EPO strategy model predicted costs similar to the autologous and allogeneic. A strategy that combines autologous blood donation with EPO for patients who cannot donate autologous blood may provide the greatest cost savings and minimize allogeneic blood transfusion.