Cost-Effectiveness Analysis of Combined Chemotherapy Regimen Containing Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis in China

Objective This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline(BR)and the conventional treatment regimen(CR,not containing Bedaquiline)for the treatment of adults with multidrug-resistant tuberculosis(MDR-TB)in China.Methods A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years.The model parameter data were synthesized from the literature,the national TB surveillance information system,and consultation with experts.The incremental cost-effectiveness ratio(ICER)of BR vs.CR was determined.Results BR(vs.CR)had a higher sputum culture conversion rate and cure rate and prevented many premature deaths(decreased by 12.8%),thereby obtaining more quality-adjusted life years(QALYs)(increased by 2.31 years).The per capita cost in BR was as high as 138,000 yuan,roughly double that of CR.The ICER for BR was 33,700 yuan/QALY,which was lower than China's 1×per capita Gross Domestic Product(GDP)in 2020(72,400 yuan).Conclusion BR is shown to be cost effective.When the unit price of Bedaquiline reaches or falls below57.21 yuan per unit,BR is expected to be the dominant strategy in China over CR.

Magnesium alloys as extremely promising alternatives for temporary orthopedic implants-A review

Mg alloys are emerging as potential and very promising alternatives for replacing permanent metallic implant materials such as steels and titanium in applications where the implants need to be removed following healing through revision surgery.Use of Mg alloys for implant application is seen as a game changer and Mg alloys are almost perfect materials for the future in both engineering and biomedical applications.Present review therefore focuses on highlighting significance of Mg alloys in biomedical field and risks of using permanent metallic implants particularly when the implants are no longer required after the injury is healed.In this review,importance of orthopedic implants in present scenario,serious concern related to accidents that are causing permanent disabilities,demand in orthopedic implant market worldwide,potential applications of Mg based materials and their compatibility in biological environment is presented and discussed.In addition,degradation rate,major reactions associated with Mg based materials and effect of alloying elements on implant performance are also discussed based on in-vivo results.Recent advances in development of Mg alloys through various techniques and their performance in in-vitro conditions are also outlined.Possible ways to eliminate the limitations of Mg alloys include alloying,melt purification,surface alterations,surface modifications,chemical treatment,secondary processing etc.are discussed.Challenges and opportunities for Mg alloys to become ideal implant material is also addressed.

Cost-effectiveness of robotic-assisted spinal surgery:A single-center retrospective study

Objective:Robotic-assisted spine surgeries(RASS)have been shown to enhance precision,reduce operative time,prevent complications,facilitate minimally invasive spinal surgery,and decrease revision surgery rates,leading to improved patient outco mes This study aimed to compare the cost-effectiveness of RAs's and non-robotic-assisted surgery for degenerative spine disease at a single center.Me thods:This retrospective study,including 122 patients,was conducted at a single center from March 2015 to February 2022.Patients who underwent ro bot-assisted surgery were assigned to the robotgroup,and patients who underwent non-robotic-assisted surgery were assigned to the non-mmbot group.Various data,indluding demographic information,surgical details,outcomes,and cost-effectiveness,were colected for both groups.The cost-effectiveness was determined using the incremental cost-effectiveness ratio(ICER),and subgroup analysis was conducted for patients with 1 or 2 levels of spi-nal instrumentation.The analysis was performed using STATA SE version 15 and Tree.Age Pro 2020,with Monte Caro simulations for the cost-effectiveness acceptability curve.Results The owerallICER was$22,572,but it decreased to$16,980 when considering cases with only 1or 2 levels of instrumentation.RASS is deemed cost-effective when the willi ingness to pay is$3000-$4000 if less than 2 levels of the spine are instrumented.Conchsions:The cost-effectiveness of robot icassistance be comes apparent whenthere isa reduced need for open surgeries,leading to decreased d revision rates caused by complications such as misplaced screwsor infctions.Therefore,it is advisable to allocate healthcare budget resou Irces to spine robots,as RASS PIDves to be cost-effective,partic cularly when only two or Ewer spinal levels require instrumentation.

Cost-effectiveness of patient specific vs conventional instrumentation for total knee arthroplasty:A systematic review and meta-analysis

BACKGROUND Over the past years,patient specific instrumentation(PSI)for total knee arthroplasty(TKA)has been implemented and routinely used.No clear answer has been given on its associated cost and cost-effectiveness when compared to conventional instrumentation(CI)for TKA.AIM To compare the cost and cost-effectiveness of PSI TKA compared to CI TKA.METHODS A literature search was performed in healthcare,economical healthcare,and medical databases(MEDLINE,EMBASE,CINAHL,Web of Science,Cochrane Library,EconLit).It was conducted in April 2021 and again in January 2022.Relevant literature included randomised controlled trials,retrospective studies,prospective studies,observational studies,and case control studies.All studies were assessed on methodological quality.Relevant outcomes included incremental cost-effectiveness ratio,quality-adjusted life years,total costs,imaging costs,production costs,sterilization associated costs,surgery duration costs and readmission rate costs.All eligible studies were assessed for risk of bias.Meta-analysis was performed for outcomes with sufficient data.RESULTS Thirty-two studies were included into the systematic review.Two were included in the metaanalysis.3994 PSI TKAs and 13267 CI TKAs were included in the sample size.The methodological quality of the included studies,based on Consensus on Health Economic Criteria-scores and risk of bias,ranged from average to good.PSI TKA costs less than CI TKA when considering mean operating room time and its associated costs and tray sterilization per patient case.PSI TKA costs more compared to CI TKA when considering imaging and production costs.Considering total costs per patient case,PSI TKA is more expensive in comparison to CI TKA.Meta-analysis comparing total costs for PSI TKA,and CI TKA showed a significant higher cost for PSI TKA.CONCLUSION Cost for PSI and CI TKA can differ when considering distinct aspects of their implementation.Total costs per patient case are increased for PSI TKA when compared to CI TKA.

Pitfalls and promises of bile duct alternatives:There is plenty of room in the regenerative surgery

Current abdominal surgery has several approaches for biliary reconstruction.However,the creation of functional and clinically applicable bile duct substitutes still represents an unmet need.In the paper by Miyazawa and colleagues,approaches to the creation of bile duct alternatives were summarized,and the reasons for the lack of development in this area were explained.The history of bile duct surgery since the nineteenth century was also traced,leading to the conclusion that the use of bioabsorbable materials holds promise for the creation of bile duct substitutes in the future.We suggest three ideas that may stimulate progress in the field of bile duct substitute creation.First,a systematic analysis of the causative factors leading to failure or success in the creation of bile duct substitutes may help to develop more effective approaches.Second,the regeneration of a bile duct is delicately balanced between epithelialization and subsequent submucosal maturation within limited time frames,which may be more apparent when using quantitative models to estimate outcomes.Third,the utilization of the organism’s endogenous regeneration abilities may enhance the creation of bile duct substitutes.We are convinced that an interdisciplinary approach,including quantitative methods,machine learning,and deep retrospective analysis of the causes that led to success and failure in studies on the creation of bile duct substitutes,holds great value.Additionally,more attention should be directed towards the balance of epithelialization and submucosal maturation rates,as well as induced angiogenesis.These ideas deserve further investigation to pave the way for bile duct restoration with physiologically relevant outcomes.

Alternative splicing of the PECTINESTERASE gene encoding a cell wall-degrading enzyme affects postharvest softening in grape

The firmness of table grape berries is a crucial quality parameter. Despite extensive research on postharvest fruit softening, its precise molecular mechanisms remain elusive. To enhance our comprehension of the underlying molecular factors, we initially identified differentially expressed genes(DEGs) by comparing the transcriptomes of folic acid(FA)-treated and water-treated(CK) berries at different time points. We then analyzed the sequences to detect alternatively spliced(AS) genes associated with postharvest softening. A total of 2,559 DEGs were identified and categorized into four subclusters based on their expression patterns, with subcluster-4 genes exhibiting higher expression in the CK group compared with the FA treatment group. There were 1,045 AS-associated genes specific to FA-treated berries and 1,042 in the CK-treated berries, respectively. Gene Ontology(GO) annotation indicated that the AS-associated genes in CK-treated berries were predominantly enriched in cell wall metabolic processes,particularly cell wall degradation processes. Through a comparison between treatment-associated AS genes and subcluster-4 DEGs, we identified eight genes, including Pectinesterase 2(VvPE2, Vitvi15g00704), which encodes a cell wall-degrading enzyme and was predicted to undergo an A3SS event. The reverse transcription polymerase chain reaction further confirmed the presence of a truncated transcript variant of VvPE2 in the FA-treated berries.Our study provides a comprehensive analysis of AS events in postharvest grape berries using transcriptome sequencing and underscores the pivotal role of VvPE2 during the postharvest storage of grape berries.

Alternate cotton-peanut intercropping:a new approach to increasing productivity and minimizing environmental impact

Recent publications have highlighted the development of an alternate cotton-peanut intercropping as a novel strat-egy to enhance agricultural productivity.In this article,we provide an overview of the progress made in the alternate cotton-peanut intercropping,specifically focusing on its yield benefits,environmental impacts,and the underlying mechanisms.In addition,we advocate for future investigations into the selection or development of appropriate crop varieties and agricultural equipment,pest management options,and the mechanisms of root-canopy interactions.This review is intended to provide a valuable reference for understanding and adopting an alternate intercropping system for sustainable cotton production.

Alternating current heating techniques for lithium-ion batteries in electric vehicles:Recent advances and perspectives

The significant decrease in battery performance at low temperatures is one of the critical challenges that electric vehicles(EVs)face,thereby affecting the penetration rate in cold regions.Alternating current(AC)heating has attracted widespread attention due to its low energy consumption and uniform heating advantages.This paper introduces the recent advances in AC heating from the perspective of practical EV applications.First,the performance degradation of EVs in low-temperature environments is introduced briefly.The concept of AC heating and its research methods are provided.Then,the effects of various AC heating methods on battery heating performance are reviewed.Based on existing studies,the main factors that affect AC heating performance are analyzed.Moreover,various heating circuits based on EVs are categorized,and their cost,size,complexity,efficiency,reliability,and heating rate are elaborated and compared.The evolution of AC heaters is presented,and the heaters used in brand vehicles are sorted out.Finally,the perspectives and challenges of AC heating are discussed.This paper can guide the selection of heater implementation methods and the optimization of heating effects for future EV applications.

Pile foundation in alternate layered liquefiable and non-liquefiable soil deposits subjected to earthquake loading

Pile foundations are still the preferred foundation system for high-rise structures in earthquake-prone regions.Pile foundations have experienced failures in past earthquakes due to liquefaction.Research on pile foundations in liquefiable soils has primarily focused on the pile foundation behavior in two or three-layered soil profiles.However,in natural occurrence,it may occur in alternative layers of liquefiable and non-liquefiable soil.However,the experimental and/or numerical studies on the layered effect on pile foundations have not been widely addressed in the literature.Most of the design codes across the world do not explicitly mention the effect of sandwiched non-liquefiable soil layers on the pile response.In the present study,the behavior of an end-bearing pile in layered liquefiable and non-liquefiable soil deposit is studied numerically.This study found that the kinematic bending moment is higher and governs the design when the effect of the sandwiched non-liquefied layer is considered in the analysis as opposed to when its effect is ignored.Therefore,ignoring the effect of the sandwiched non-liquefied layer in a liquefiable soil deposit might be a nonconservative design approach.

A Neural-network-based Alternative Scheme to Include Nonhydrostatic Processes in an Atmospheric Dynamical Core

Here,a nonhydrostatic alternative scheme(NAS)is proposed for the grey zone where the nonhydrostatic impact on the atmosphere is evident but not large enough to justify the necessity to include an implicit nonhydrostatic solver in an atmospheric dynamical core.The NAS is designed to replace this solver,which can be incorporated into any hydrostatic models so that existing well-developed hydrostatic models can effectively serve for a longer time.Recent advances in machine learning(ML)provide a potential tool for capturing the main complicated nonlinear-nonhydrostatic relationship.In this study,an ML approach called a neural network(NN)was adopted to select leading input features and develop the NAS.The NNs were trained and evaluated with 12-day simulation results of dry baroclinic-wave tests by the Weather Research and Forecasting(WRF)model.The forward time difference of the nonhydrostatic tendency was used as the target variable,and the five selected features were the nonhydrostatic tendency at the last time step,and four hydrostatic variables at the current step including geopotential height,pressure in two different forms,and potential temperature,respectively.Finally,a practical NAS was developed with these features and trained layer by layer at a 20-km horizontal resolution,which can accurately reproduce the temporal variation and vertical distribution of the nonhydrostatic tendency.Corrected by the NN-based NAS,the improved hydrostatic solver at different horizontal resolutions can run stably for at least one month and effectively reduce most of the nonhydrostatic errors in terms of system bias,anomaly root-mean-square error,and the error of the wave spatial pattern,which proves the feasibility and superiority of this scheme.

Improved genome annotation of Brassica oleracea highlights the importance of alternative splicing

Brassica oleracea has been developed into many important crops,including cabbage,kale,cauliflower,broccoli and so on.The genome and gene annotation of cabbage(cultivar JZS),a representative morphotype of B.oleracea,has been widely used as a common reference in biological research.Although its genome assembly has been updated twice,the current gene annotation still lacks information on untranslated regions(UTRs)and alternative splicing(AS).Here,we constructed a high-quality gene annotation(JZSv3)using a full-length transcriptome acquired by nanopore sequencing,yielding a total of 59452 genes and 75684 transcripts.Additionally,we re-analyzed the previously reported transcriptome data related to the development of different tissues and cold response using JZSv3 as a reference,and found that 3843 out of 11908 differentially expressed genes(DEGs)underwent AS during the development of different tissues and 309 out of 903 cold-related genes underwent AS in response to cold stress.Meanwhile,we also identified many AS genes,including BolLHCB5 and BolHSP70,that displayed distinct expression patterns within variant transcripts of the same gene,highlighting the importance of JZSv3 as a pivotal reference for AS analysis.Overall,JZSv3 provides a valuable resource for exploring gene function,especially for obtaining a deeper understanding of AS regulation mechanisms.

Wetting alternating with partial drying during grain filling increases lysine biosynthesis in inferior rice grain

Lysine content is a criterion of the nutritional quality of rice.Understanding the process of lysine biosynthesis in early-flowering superior grain(SG)and late-flowering inferior grain(IG)of rice would advance breeding and cultivation to improve nutritional quality.However,little information is available on differences in lysine anabolism between SG and IG and the underlying mechanism,and whether and how irrigation regimes affect lysine anabolism in these grains.A japonica rice cultivar was grown in the field and two irrigation regimes,continuous flooding(CF)and wetting alternating with partial drying(WAPD),were imposed from heading to the mature stage.Lysine content and activities of key enzymes of lysine biosynthesis,and levels of brassinosteroids(BRs)were lower in the IG than in the SG at the early grainfilling stage but higher at middle and late grain-filling stages.WAPD increased activities of these key enzymes,BR levels,and contents of lysine and total amino acids in IG,but not SG relative to CF.Application of 2,4-epibrassinolide to rice panicles in CF during early grain filling reproduced the effects of WAPD,but neither treatment altered the activities of enzymes responsible for lysine catabolism in either SG or IG.WAPD and elevated BR levels during grain filling increased lysine biosynthesis in IG.Improvement in lysine biosynthesis in rice should focus on IG.

Cost-effectiveness Analysis of Insulin Degludec and Liraglutide Injection in the Treatment of Type 2 Diabetes

Objective To analyze the cost-effectiveness of insulin degludec and liraglutide injection(IDegLira)compared with insulin glargine plus insulin aspart(IGar plus IAsp)in the treatment of type 2 diabetes mellitus(T2DM)based on the price of IDegLira before and after it was successfully admitted to the National Reimbursable Drug List(NRDL).Methods Cost and effectiveness parameters were obtained through systematic retrieval from PubMed,ScienceDirect,CNKI,and Wanfang database.A cost-effectiveness analysis(CEA)model was established to analyze the economics using IDegLira for T2DM patients with 1 to 5 years of medication.Results and Conclusion Before IDegLira was admitted to NRDL,its economic advantages over the IGlar plus Iasp regimen became more significant as patients’medication time prolonged.After being admitted to NRDL,with 1 year of medication,the medical cost of IDegLira decreased by 2853.91 yuan and the quality adjusted life years(QALY)increased by 0.12055 than IGar plus IAsp.The sensitivity analysis was highly consistent with the results of the baseline result.After being admitted to NRDL,for patients with T2DM who have poor blood glucose control,IDegLira is absolutely an economic advantage scheme compared with IGar plus IAsp.

2,3,5,4’-Tetrahydroxystilbene-2-O-b-D-Glucoside modulates CHEK2 and CCND1 alternative splicing to inhibit MCF-7 cells proliferation

Background:In our previous study,we observed a synergistic effect of 2,3,5,4’-Tetrahydroxystilbene-2-O-b-D-glucoside combined with adriamycin to induce apoptosis in MCF-7 breast cancer cells.However,the underlying mechanisms of epigenetic modifications,such as alternative splicing,have not been explored.In this study,we aimed to investigate the mechanism by which THSG inhibits MCF-7 cell proliferation using full-length transcriptome sequencing.Methods:First,cell viability was examined using the methyl thiazolyl tetrazolium method and full-length transcriptome sequencing was performed to identify genes and pathways.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to identify the principal pathways and targets of THSG.Flow cytometry analysis of cell cycle distribution was performed.Meanwhile,the analysis of alternative splicing and domains of the key proteins was conducted.Quantitative polymerase chain reaction and western blotting were performed for verification.Results:THSG showed significant cytotoxic activity in MCF-7 cells.Full-length transcriptome sequencing revealed differential alternative splicing with 173 upregulated and 263 downregulated genes.Further analysis identified distinct differential expression of genes(CHEK2-211 and CCND1-201)involved in the cell cycle in the THSG-treated group.Subsequently,alternative splicing types of CHEK2(mutually exclusive exon)and CCND1(intron retention).We found that THSG downregulated mRNA expression,as confirmed by quantitative polymerase chain reaction analysis.Interestingly,protein structural analysis revealed that THSG treatment led to the generation of CHK2-211,which was the result of a mutation in the amino acid residues(GLU-150,ASN-151)of the CHEK2 domain(VAL-150,GLY-151).and CyclinD1-201 were obtained when an amino acid(ASP-267)in the domain was lost in CyclinD1.Moreover,molecular docking analysis demonstrated that the domains of key proteins could bind THSG more effectively,with no difference in affinity.Western blotting confirmed that THSG inhibited the expression of CHK2 and CyclinD1.Conclusion:THSG modulated the alternative splicing of CHEK2 and CCND1 by inducing G0/G1 cell cycle arrest,consequently suppressing MCF-7 cell proliferation.

Suppression of stimulated Brillouin and Raman scatterings using an alternating frequency laser and transverse magnetic fields

A novel scheme to suppress both stimulated Brillouin scattering(SBS) and stimulated Raman scattering(SRS) by combining an alternating frequency(AF) laser and a transverse magnetic field is proposed. The AF laser allows the laser frequency to change discretely and alternately over time. The suppression of SBS is significant as long as the AF difference is greater than the linear growth rate of SBS or the alternating time of the laser frequency is shorter than the linear growth time of SBS. However, the AF laser proves ineffective in suppressing SRS, which usually has a much higher linear growth rate than SBS. To remedy that, a transverse magnetic field is included to suppress the SRS instability. The electrons trapped in the electron plasma waves(EPWs) of SRS can be accelerated by the surfatron mechanism in a transverse magnetic field and eventually detrapped. While continuously extracting energy from EPWs, the EPWs are dissipated and the kinetic inflation of SRS is suppressed. The one-dimensional particle-in-cell simulation results show that both SBS and SRS can be effectively suppressed by combining the AF laser with a transverse magnetic field with tens of Tesla. The total reflectivity can be dramatically reduced by more than one order of magnitude. These results provide a potential reference for controlling SBS and SRS under the related parameters of inertial confinement fusion.

Workshop “Navigating the Transition: Standards Powering the Journey of Alternative Fuel Infrastructure”

April 18, Brussels, Belgium In light of recent significant regulatory changes within the European Union impacting the transport sector, such as the Alternative Fuels Infrastructure Regulation(AFIR), Re Fuel EU and Fuel EU Maritime, the role of European standardization becomes increasingly critical in facilitating the transition towards the deployment of alternative fuels.

Diagnosing ratio of electron density to collision frequency of plasma surrounding scaled model in a shock tube using low-frequency alternating magnetic field phase shift

A non-contact low-frequency(LF)method of diagnosing the plasma surrounding a scaled model in a shock tube is proposed.This method utilizes the phase shift occurring after the transmission of an LF alternating magnetic field through the plasma to directly measure the ratio of the plasma loop average electron density to collision frequency.An equivalent circuit model is used to analyze the relationship of the phase shift of the magnetic field component of LF electromagnetic waves with the plasma electron density and collision frequency.The applicable range of the LF method on a given plasma scale is analyzed.The upper diagnostic limit for the ratio of the electron density(unit:m^(-3))to collision frequency(unit:Hz)exceeds 1×10^(11),enabling an electron density to exceed 1×10^(20)m^(-3)and a collision frequency to be less than 1 GHz.In this work,the feasibility of using the LF phase shift to implement the plasma diagnosis is also assessed.Diagnosis experiments on shock tube equipment are conducted by using both the electrostatic probe method and LF method.By comparing the diagnostic results of the two methods,the inversion results are relatively consistent with each other,thereby preliminarily verifying the feasibility of the LF method.The ratio of the electron density to the collision frequency has a relatively uniform distribution during the plasma stabilization.The LF diagnostic path is a loop around the model,which is suitable for diagnosing the plasma that surrounds the model.Finally,the causes of diagnostic discrepancy between the two methods are analyzed.The proposed method provides a new avenue for diagnosing high-density enveloping plasma.

Use of Topical Complementary and Alternative Medicines (CAM) in Diabetic Septic Foot Disease in Makkah Region, Western of Saudi Arabia, an Exploratory Study

Diabetes is a chronic condition that is significantly impacted daily by environment. At least one in five Saudis, suffer from diabetes. “Diabetes is a pandemic of unprecedented magnitude spiraling out of control” (Boulton). Saudi Arabia ranks the second highest in the Middle East, and is the seventh in the world for the prevalence of diabetes (WHO). Diabetes mellitus (DM) has been found to be related to high mortality, morbidity accompanied by poor general health and lower quality of life. Current Saudi diabetes patients’ behaviors, practices, and beliefs regarding foot health problems such as ulcers, are not well investigated. Diabetic patients frequently utilize natural remedies and Herbs for self-medication as a part of complementary and alternative Medicine. Aim of study: To explore the widespread use of the alternative remedies in the local communities of the Western Saudi Arabia, the drives behind using and to focus on the potential adverse effects following their usage. Method: A descriptive, cross-sectional study of 386 diabetic patients with feet problems in Makkah Region, West of Saudi Arabia during the period April - June 2023. Results: Out of the 531 participants, only 386 participants reported diabetic foot disorder (DFD). Most of the participant were above 65 years of age group (24.61 %). Male (52.08%) more than female (47.92%) in the research group. All of the participants had diabetic foot disorders at least once. The prevalence of complementary and alternative medicines (CAM) use among them was 67.88%, as solitary or in combination with hospital medicines. Honey headed the list followed by myrrh and black seeds. Acquaintances advice (59.54%) was the most reason for using the alternative medicine. 60.30% of Diabetic foot patient complained of adverse effects during CAM remedies use. Conclusion: Consumption of CAM remedies among diabetic patients for Diabetic Foot Disorder (DFD) is common. Honey headed the list followed by myrrh and black seeds. Additional wide-scale research is required to establish their actual efficacy, safety and potential adverse out-comes and to generalize the outcomes.

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer

Metastasis remains a major challenge in the successful management of malignant diseases.The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,stomach,and pancreatic cancers,as well as melanoma,breast cancer,and sarcoma.As an important factor that influences the development of metastatic liver cancer,alternative splicing drives the diversity of RNA transcripts and protein subtypes,which may provide potential to broaden the target space.In particular,the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence,progression,aggressiveness,and drug resistance of cancers caused by the selective splicing of specific genes.This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer.It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes,abnormal splicing,and the contribution of hypoxia to these changes during metastasis.

High-resolution microendoscopy for esophageal cancer screening in China: A cost-effectiveness analysis

AIM:To study the cost-effectiveness of high-resolution microendoscopy(HRME)in an esophageal squamous cell carcinoma(ESCC)screening program in China.METHODS:A decision analytic Markov model of ESCC was developed.Separate model analyses were conducted for cohorts consisting of an averagerisk population or a high-risk population in China.Hypothetical 50-year-old individuals were followed until age 80 or death.We compared three different strategies for both cohorts:(1)no screening;(2)standard endoscopic screening with Lugol’s iodine staining;and(3)endoscopic screening with Lugol’s iodine staining and an HRME.Model parameters were estimated from the literature as well as from GLOBOCAN,the Cancer Incidence and Mortality Worldwide cancer database.Health states in the model included non-neoplasia,mild dysplasia,moderate dysplasia,high-grade dysplasia,intramucosal carcinoma,operable cancer,inoperable cancer,and death.Separate ESCC incidence transition rates were generated for the average-risk and high-risk populations.Costs in Chinese currency were converted to international dollars(I$)and were adjusted to 2012dollars using the Consumer Price Index.RESULTS:The main outcome measurements for this study were quality-adjusted life years(QALYs)and incremental cost-effectiveness ratio(ICER).For the average-risk population,the HRME screening strategy produced 0.043 more QALYs than the no screening strategy at an additional cost of I$646,resulting in an ICER of I$11808 per QALY gained.Standard endoscopic screening was weakly dominated.Among the high-risk population,when the HRME screening strategy was compared with the standard screening strategy,the ICER was I$8173 per QALY.For both the high-risk and average-risk screening populations,the HRME screening strategy appeared to be the most cost-effective strategy,producing ICERs below the willingness-topay threshold,I$23500 per QALY.One-way sensitivity analysis showed that,for the average-risk population,higher specificity of Lugol’s iodine(>40%)and lower specificity of HRME(<70%)could make Lugol’s iodine screening cost-effective.For the high-risk population,the results of the model were not substantially affected by varying the follow-up rate after Lugol’s iodine screening,Lugol’s iodine test characteristics(sensitivity and specificity),or HRME specificity.CONCLUSION:The incorporation of HRME into an ESCC screening program could be cost-effective in China.Larger studies of HRME performance are needed to confirm these findings.