Is circulating tumor cell count-driven cost-effective for first-line therapy choice in HR+/HER2- metastatic breast cancer in the United States?

BACKGROUND: Circulating tumor cell (CTC) counting may be a useful non-invasive biomarker that helps patients choose first-line treatment options. Nevertheless, the cost of CTC inspection may impose an economic burden on patients, necessitating the simultaneous consideration of both its clinical effectiveness and cost. We evaluated the cost-effectiveness of CTC count-guided chemotherapy and endocrine therapy as first-line therapy for HR+/HER2-metastatic breast cancer (MBC) from the perspective of US payers. METHODS: Based on the STIC CTC trial, a Markov model was constructed for three health states, and health outcomes were measured in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to assess the robustness of the incremental cost per QALY. RESULTS: The base-case analysis revealed that CTC count-driven treatment was associated with improved effectiveness by 0.07 QALYs and increased the overall cost by $9187.05 compared with clinician-driven first-line treatment choices, leading to an ICER of $138 354.15 per QALY. One-way sensitivity analysis indicated that the model was most sensitive to the cost of treatment for neutropenia and the utility for PFS; probability sensitivity analysis indicated that CTC count-driven treatment choices would be considered the cost-effective option at a willingness-to-pay threshold of $150 000 per QALY. CONCLUSIONS: The findings of this cost-effectiveness analysis suggest that, at the current price of CTC enumeration, choosing first-line treatment options based on CTC count is a cost-effectiveness approach for treating patients with HR+/HER2- MBC in the US.

Engineering Low-Cost Organic Cathode for Aqueous Rechargeable Battery and Demonstrating the Proton Intercalation Mechanism for Pyrazine Energy Storage Unit.

Seeking organic cathode materials with low cost and long cycle life that can be employed for large-scale energy storage remains a significant challenge. This work has synthesized an organic compound, triphenazino[2,3-b](1,4,5,8,9,12-hexaazatriphenylene) (TPHATP), with as high as 87.16% yield. This compound has a highly π-conjugated and rigid molecular structure, which is synthesized by capping hexaketocyclohexane with three molecules of 2,3-diaminophenazine derived from low-cost o-phenylenediamine, and is used as a cathode material for assembling aqueous rechargeable zinc ion batteries. Both experiments and DFT calculations demonstrate that the redox mechanism of TPHATP is predominantly governed by H+ storage. The Zn-intercalation product of nitride-type compound, is too unstable to form in water. Moreover, the TPHATP cathode exhibits a capacity of as high as 318.3 mAh g-1 at 0.1 A g-1 , and maintained a stable capacity of 111.9 mAh g-1 at a large current density of 10 A g-1 for 5000 cycles with only a decay of 0.000512% per cycle. This study provides new insights into understanding pyrazine as an active redox group and offers a potential affordable aqueous battery system for grid-scale energy storage.

Longitudinal assessment of placental perfusion in normal and hypertensive pregnancies using pseudo-continuous arterial spin-labeled MRI: preliminary experience.

OBJECTIVES: To evaluate longitudinal placental perfusion using pseudo-continuous arterial spin-labeled (pCASL) MRI in normal pregnancies and in pregnancies affected by chronic hypertension (cHTN), who are at the greatest risk for placental-mediated disease conditions. METHODS: Eighteen normal and 23 pregnant subjects with cHTN requiring antihypertensive therapy were scanned at 3 T using free-breathing pCASL-MRI at 16-20 and 24-28 weeks of gestational age. RESULTS: Mean placental perfusion was 103.1 ± 48.0 and 71.4 ± 18.3 mL/100 g/min at 16-20 and 24-28 weeks respectively in normal pregnancies and 79.4 ± 27.4 and 74.9 ± 26.6 mL/100 g/min in cHTN pregnancies. There was a significant decrease in perfusion between the first and second scans in normal pregnancies (p = 0.004), which was not observed in cHTN pregnancies (p = 0.36). The mean perfusion was not statistically different between normal and cHTN pregnancies at both scans, but the absolute change in perfusion per week was statistically different between these groups (p = 0.044). Furthermore, placental perfusion was significantly lower at both time points (p = 0.027 and 0.044 respectively) in the four pregnant subjects with cHTN who went on to have infants that were small for gestational age (52.7 ± 20.4 and 50.4 ± 20.9 mL/100 g/min) versus those who did not (85 ± 25.6 and 80.0 ± 25.1 mL/100 g/min). CONCLUSION: pCASL-MRI enables longitudinal assessment of placental perfusion in pregnant subjects. Placental perfusion in the second trimester declined in normal pregnancies whereas it remained unchanged in cHTN pregnancies, consistent with alterations due to vascular disease pathology. Perfusion was significantly lower in those with small for gestational age infants, indicating that pCASL-MRI-measured perfusion may be an effective imaging biomarker for placental insufficiency. CLINICAL RELEVANCE STATEMENT: pCASL-MRI enables longitudinal assessment of placental perfusion without administering exogenous contrast agent and can identify placental insufficiency in pregnant subjects with chronic hypertension that can lead to earlier interventions. KEY POINTS: • Arterial spin-labeled (ASL) magnetic resonance imaging (MRI) enables longitudinal assessment of placental perfusion without administering exogenous contrast agent. • ASL-MRI-measured placental perfusion decreased significantly between 16-20 week and 24-28 week gestational age in normal pregnancies, while it remained relatively constant in hypertensive pregnancies, attributed to vascular disease pathology. • ASL-MRI-measured placental perfusion was significantly lower in subjects with hypertension who had a small for gestational age infant at 16-20-week gestation, indicating perfusion as an effective biomarker of placental insufficiency.

Global burden of rabies in 204 countries and territories, from 1990 to 2019: results from the Global Burden of Disease Study 2019.

OBJECTIVES: Rabies is an acute lethal infectious disease caused by a lyssavirus infection. In 2018, the World Health Organization proposed a global strategic plan to end human rabies deaths by 2030. However, systematic studies on the global rabies disease burden and epidemiological trends are scarce. METHODS: We extracted the disease burden and epidemiological data of rabies worldwide in the preceding 30 years from the Global Burden of Disease Study 2019 and performed a comprehensive analysis. RESULTS: In 2019, the incident cases of rabies worldwide were 14,075.51 (95% uncertainty interval: 6124.33-21,618.11), and the number of deaths was 13,743.44 (95% uncertainty interval: 6019.13-17,938.53), both of which were lower than that in 1990. With the improvement of the sociodemographic index, the incident cases, the number of deaths, age-standardized incidence rate, age-standardized incidence death rate, and disability-adjusted life years of rabies all showed downward trends. Adolescents and adults aged <50 years represented the majority of rabies cases worldwide. CONCLUSION: The global disease burden of rabies has declined over the past 30 years. Furthermore, the disease burden of rabies was closely related to the sociodemographic index level.

Using Deep Neural Network Approach for Multiple-Class Assessment of Digital Mammography.

According to the Health Promotion Administration in the Ministry of Health and Welfare statistics in Taiwan, over ten thousand women have breast cancer every year. Mammography is widely used to detect breast cancer. However, it is limited by the operator's technique, the cooperation of the subjects, and the subjective interpretation by the physician. It results in inconsistent identification. Therefore, this study explores the use of a deep neural network algorithm for the classification of mammography images. In the experimental design, a retrospective study was used to collect imaging data from actual clinical cases. The mammography images were collected and classified according to the breast image reporting and data-analyzing system (BI-RADS). In terms of model building, a fully convolutional dense connection network (FC-DCN) is used for the network backbone. All the images were obtained through image preprocessing, a data augmentation method, and transfer learning technology to build a mammography image classification model. The research results show the model's accuracy, sensitivity, and specificity were 86.37%, 100%, and 72.73%, respectively. Based on the FC-DCN model framework, it can effectively reduce the number of training parameters and successfully obtain a reasonable image classification model for mammography.

Analysis of the Future Evolution of Biocapacity and Landscape Characteristics in the Agro-Pastoral Zone of Northern China.

The Agro-Pastoral Zone of Northern China (AZNC) is an ecologically fragile zone. It is a challenge to create scientifically sound plans for environmental conservation and agro-pastoral development due to the lack of future evolution prediction, and analysis of biocapacity (BC) and landscape characteristics. Using the Globeland30 dataset from 2000 to 2020, this study simulated 2030 land use/land cover (LULC) scenarios, and analyzed the future evolution of BC and landscape patterns. The results show that: (1) The Logistic and CA-Markov models can reasonably simulate the LULC changes in the research area, with ROC indices over 0.9 and Kappa approaching 0.805, after considering the driving factors such as physical geography, regional climate, and socio-economic development. (2) From 2000 to 2030, the spatial distribution pattern of LULC does not change significantly, and cultivated land, grassland, and forest are still the dominant land types in the research area. The regional BC exhibits an increasing trend (+4.55 × 106 gha/a), and the spatial distribution pattern of BC is similar to that of LULC. (3) Changes in land miniaturization, landscape fragmentation, and decreased aggregation can be seen in the entire AZNC and specific land categories, including cultivated land, grassland, and forest. The study provides suggestions for formulating the AZNC's future ecological protection and agro-pastoral development strategies, and guidance for the LULC simulation in other agro-pastoral zones.

Analysis of long non-coding RNA expression profile of bovine monocyte-macrophage infected by Mycobacterium avium subsp. paratuberculosis.

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of paratuberculosis. As a potential zoonotic pathogen, MAP also seriously threatens human health and social security. At present, long non-coding RNA (lncRNA) has attracted wide attention as an useful biomarker in various diseases. Therefore, our study analyzed the lncRNA expression profiles and lncRNA-mRNA regulatory network of MAP infected bovine monocytes-macrophages and uninfected bovine cells by high-throughput sequencing. A total of 4641 differentially expressed lncRNAs genes were identified, including 3111 up-regulated genes and 1530 down-regulated genes. In addition, lncRNA-mRNA interaction analysis was performed to predict the target genes of lncRNA. Among them, after MAP infection, 86 lncRNAs targeted to mRNA, of which only 6 genes were significantly different. The results of Gene Ontology (GO) enrichment analysis showed that the differentially expressed genes significantly enriched in functional groups were related to immune regulation. Multiple signal pathways including NF-κB, NOD-like receptor, Cytokine-cytokine receptor, Toll-like receptor signaling pathway, Chemokine signaling pathway, and other important biochemical, metabolic and signal transduction pathways were enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG). In this study, analysis of macrophage transcriptomes in response to MAP infection is expected to provide key information to deeply understand role of the pathogen in initiating an inappropriate and persistent infection in susceptible hosts and molecular mechanisms that might underlie the early phases of paratuberculosis.

A novel immune-related long non-coding RNAs risk model for prognosis assessment of lung adenocarcinoma.

BACKGROUND: The abundant immune-related long non-coding RNA (IRLNRs) in immune cells and immune microenvironment have the potential to forecast prognosis and evaluate the effect of immunotherapy. IRLNRs analysis will provide a new perspective for LUAC research. METHODS: We calculated the immune score of each sample according to the expression levels of immune-related genes (IRGs) and screened the survival-related IRLNRs (sIRLNRs) by Cox regression analysis. The expression levels of AC068338.3 and AL691432.2 in tissues and cell lines were confirmed by RT-qPCR. RESULTS: 36 IRLNRs were selected by Pearson correlation analysis. Ten sIRLNRs were significantly correlated with the clinical outcomes of LUAC patients. Five sIRLNRs were identified by multivariate COX regression analysis to establish the immune-related risk score model (IRRS). The overall survival (OS) in the high-risk group was shorter than that in the low-risk group. IRRS could be an independent prognostic factor with significant survival correlation The distributions of immune gene concentrations were different between high-risk group and low-risk group. Furthermore, we further verified that the expression levels of AC068338.3 and AL691432.2 in different LUAC cell lines and tumor tissues were lower than that in Human bronchial epithelial cell (HBE) and adjacent tissues respectively. The lower expression levels of AC068338.3 and AL691432.2 were detected with the more advance T-stages. CONCLUSIONS: Our results highlighted some sIRLNRs with significant clinical correlations and demonstrated their monitored and prognostic values for LUAC patients. The results of this study may provide a new perspective for immunological research and immunotherapy strategies.

In vitro assessment and phase I randomized clinical trial of anfibatide a snake venom derived anti-thrombotic agent targeting human platelet GPIbα.

The interaction of platelet GPIbα with von Willebrand factor (VWF) is essential to initiate platelet adhesion and thrombosis, particularly under high shear stress conditions. However, no drug targeting GPIbα has been developed for clinical practice. Here we characterized anfibatide, a GPIbα antagonist purified from snake (Deinagkistrodon acutus) venom, and evaluated its interaction with GPIbα by surface plasmon resonance and in silico modeling. We demonstrated that anfibatide interferds with both VWF and thrombin binding, inhibited ristocetin/botrocetin- and low-dose thrombin-induced human platelet aggregation, and decreased thrombus volume and stability in blood flowing over collagen. In a single-center, randomized, and open-label phase I clinical trial, anfibatide was administered intravenously to 94 healthy volunteers either as a single dose bolus, or a bolus followed by a constant rate infusion of anfibatide for 24 h. Anfibatide inhibited VWF-mediated platelet aggregation without significantly altering bleeding time or coagulation. The inhibitory effects disappeared within 8 h after drug withdrawal. No thrombocytopenia or anti-anfibatide antibodies were detected, and no serious adverse events or allergic reactions were observed during the studies. Therefore, anfibatide was well-tolerated among healthy subjects. Interestingly, anfibatide exhibited pharmacologic effects in vivo at concentrations thousand-fold lower than in vitro, a phenomenon which deserves further investigation.Trial registration: Clinicaltrials.gov NCT01588132.

Automatic assessment of bone age in Taiwanese children: A comparison of the Greulich and Pyle method and the Tanner and Whitehouse 3 method.

Proper bone age assessment is crucial for the clinical diagnosis and evaluation of treatment responses. We investigated the applicability of Greulich and Pyle (GP), and Tanner and Whitehouse 3 (TW3) methods for children in modern Taiwan, using computer-aided diagnosis. Hand and wrist radiographs were obtained from 611 children (3-17 years) who came to our emergency department due to trauma. Ages 0 to 2 years old were excluded because of a limited number of cases. Skeletal maturation was assessed using the BoneXpert (version 2.5.4.1 automated software), which determines GP and TW3 bone age. The two scoring systems were evaluated for comparing the chronological ages in each subgroup. In boys, mean GP bone age vs mean chronological ages were delayed for ages 3 to 11 and advanced for age 12 to 17. In girls, mean GP bone age vs mean chronological ages was delayed for ages 4 to 8 and 17, and advanced for ages 3 and 9 to 17. In boys, the mean TW3 bone ages vs mean chronological ages were delayed for ages 5 to 10 except age 8, and advanced for ages 3 to 4, 8, and 11 to 15. In girls, the mean TW3 bone ages vs mean chronological ages were delayed for ages 4 to 12, and advanced for ages 3 and 13 to 14. By using the BoneXpert automatic software, we established bone age reference standards for children in Taiwan. Clinical application of GP and TW3 scoring methods can be adjusted according to our results to better assess bone age.

The Influence of Land Use Change on Ecosystem Service Value in Shangzhou District.

Land use change has an impact on the ecosystem service value because it changes the structure and function of ecosystems. This paper analyzed the changes in land use during the period from 2000 to 2015 in Shangzhou district, and used the equivalent value of ecological services per unit area of land ecosystem combining the natural and economic conditions of Shangzhou district. Based on this method, the ecological service value of Shangzhou district was estimated, and the impact of land use change on the ecological service value was analyzed. The results showed that: (1) the main types of land use in Shangzhou district were grassland, woodland and farmland, among which the contribution rate of woodland to the value of local ecosystem services was the highest; (2) the overall trend in the ecosystem service value in Shangzhou district increased between 2000 and 2015, from 10.74 × 108 yuan in 2000 to 20.32 × 108 yuan in 2015, which is the result of the combined effects of regional economic development and changes in the natural environment and land use patterns; and (3) the main reason for the value increase of ecosystem services in Shangzhou district between 2000 and 2015 was that the grain-for-green policy transformed a considerable amount of farmland into woodland, while the main reasons for a decline in value was the expansion of built-up land that occupied other types of land.

Regional Cerebral Blood Flow in Mania: Assessment Using 320-Slice Computed Tomography.

Objectives: While evidence that episodes of mania in bipolar I are associated with changes in bioenergetic and regional cerebral blood flow (rCBF) and cerebral blood flow velocity (rCBFV), both the regions and the extent of these changes have not yet been defined. Therefore, we determined the pattern of regional cerebral perfusion mania patients and using patients with major depressive disorder (MDD) as positive controls and healthy participants as negative controls. Methods: Twenty participants with mania, together with 22 MDD patients and 24 healthy volunteers, were recruited for this study. On all participants, Transcranial Doppler (TCD) was conducted to measure rCBFV parameters, 320-slice CT was conducted to measure rCBF in the different cerebral artery regions, and hematological parameters were assessed. ANOVA and Pearson's tests were used for the statistical analysis. Results: Our data indicated that rCBF in the medial temporal lobe and hippocampus, especially in the left medial temporal lobe and the right hippocampus, was increased in the mania group compared with the control and MDD groups (p < 0.01). In contrast, rCBF in the medial temporal lobe and hippocampus was decreased in the depression group (p < 0.01) compared with healthy controls. In addition, values of rCBFV in the bilateral internal carotid arteries (ICAs) and middle cerebral arteries (MCA) were increased in mania (p < 0.01) in comparison to the MDD group. Whole blood viscosity and hematocrit as well as red blood cell sedimentation rate remained unchanged in all group (p > 0.05). Conclusions: In mania, rCBF is increased in the medial temporal lobe and hippocampus, with a corresponding increase in rCBFV in the same regions.

Disease characteristics and management of hospitalised adolescents and adults with community-acquired pneumonia in China: a retrospective multicentre survey.

OBJECTIVES: To describe the clinical characteristics and management of patients hospitalised with community-acquired pneumonia (CAP) in China. DESIGN: This was a multicentre, retrospective, observational study. SETTING: 13 teaching hospitals in northern, central and southern China from 1 January 2014 to 31 December 2014 PARTICIPANTS: Information on hospitalised patients aged ≥14 years with radiographically confirmed pneumonia with illness onset in the community was collected using standard case report forms. PRIMARY AND SECONDARY OUTCOME MEASURES: Resource use for CAP management. RESULTS: Of 14 793 patients screened, 5828 with radiographically confirmed CAP were included in the final analysis. Low mortality risk patients with a CURB-65 score 0-1 and Pneumonia Severity Index risk class I-II accounted for 81.2% (4434/5594) and 56.4% (2034/3609) patients, respectively. 21.7% (1111/5130) patients had already achieved clinical stability on admission. A definite or probable pathogen was identified only in 12.7% (738/5828) patients. 40.9% (1575/3852) patients without pseudomonal infection risk factors received antimicrobial overtreatment regimens. The median duration between clinical stability to discharge was 5.0 days with 30-day mortality of 4.2%. CONCLUSIONS: These data demonstrated the overuse of health resources in CAP management, indicating that there is potential for improvement and substantial savings to healthcare systems in China. TRIAL REGISTRATION NUMBER: NCT02489578; Results.

Translation and validation of the Chinese Social Role Participation Questionnaire in patients with ankylosing spondylitis.

Social Role Participation Questionnaire (SRPQ) is used to evaluate the social participation with ankylosing spondylitis (AS). Although the SRPQ has English and Dutch versions, there is no Chinese version even though China has the largest population of patients with AS. The objective of our study was to translate the SRPQ into Chinese version and assess its reliability and validity in Chinese patients with AS. The C-SRPQ was developed in a five-step translation and cross-cultural adaptation procedure. A total of 105 patients with AS were recruited during the time from September 2014 to June 2017. The intraclass correlation coefficient (ICC), Cronbach's alpha (α), and Spearman correlation coefficient (r) were used to evaluate test-retest reliability, internal consistency reliability, and the construct validity of C-SRPQ, respectively. All of the 105 patients with AS successfully completed the questionnaires. Ninety-eight patients (93.33%) participated in at least nine roles for satisfaction dimensions. No floor or ceiling effects were checked. The high value of ICC (> 0.8, 0.831-0.895) indicated the excellent test-retest reliability. In internal consistency reliability, most of Cronbach's alpha coefficient was strong (α ≥ 0.7, 0.534-0.962). In construct validity, more than half of the correlations between the dimensions of C-SRPQ and other questionnaires were good (r > 0.6). The correlations between all dimensions of C-SRPQ and BASDAI, BASFI, and ASQoL were strong negative (P < 0.01). There was a strong positive correlation (P < 0.01) between all dimensions of C-SRPQ and SF-36 physical component score (SF-36PCS), SF-36 mental component role score (SF-36MCS). The C-SRPQ is a reliable and valid questionnaire to evaluate the social participation in Chinese patients with AS.

Assessment of radiotherapy combined with adjuvant chemotherapy in the treatment of patients with advanced nasopharyngeal carcinoma: a prospective study.

PURPOSE: To explore the clinical efficacy of radiotherapy combined with concurrent combination chemotherapy in the treatment of patients with advanced nasopharyngeal carcinoma (NPC). METHODS: Two hundred patients with stage III/IV NPC were randomly allocated into the treatment group (N=100) and the control group (N=100). Patients in the control group received conventional fractionated radiotherapy, while patients in the treatment group received conventional fractionated radiotherapy combined with concurrent combination chemotherapy with cisplatin and 5-fluorouracil (5-FU). Short-term efficacy, radiotherapy toxicity, shortand long-term survival were compared. RESULTS: The short-term response rate of the treatment group was 96%, which was significantly higher than that of the control group (87%, p<0.05). The local radiation toxicity of the treatment group was similar to that of the control group p>0.05), but the hematological and gastrointestinal toxicities were significantly higher in the treatment group p<0.05). The 1-, 3- and 5-year overall survival rates were 87, 80, and 76%, respectively, in the treatment group and 74, 64, and 51%, respectively, in the control group, significantly favoring the treatment group p<0.05). CONCLUSION: Radiotherapy with concurrent combination chemotherapy can improve the prognosis of patients with advanced NPC but at the cost of significant toxicity.

Steaming-induced chemical transformations and holistic quality assessment of red ginseng derived from Panax ginseng by means of HPLC-ESI-MS/MS(n)-based multicomponent quantification fingerprint.

The purpose of this study is to evaluate the steaming-induced chemical transformation of red ginseng manufactured from fresh ginseng by means of simultaneous quantitative and qualitative analyses with a combinative high-performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI-MS/MS(n)) technique. Thirty-six ginsenosides were identified in red ginseng and white ginseng by comparing the mass spectrum and/or matching the empirical molecular formula with that of known published compounds, and 11 of them were determined to be newly generated during the red ginseng preparatory process. The mechanisms involved were further deduced to be hydrolysis, dehydration, isomerization, and decarboxylation at C-20, and hydrolysis also occurs at C-3 or C-6 of the original ginsenosides through the mimic process of steaming and heating in laboratory. The multicomponent quantification fingerprint of ginseng was also established by HPLC-UV method, and the contents of 12 ginsenosides in red and white ginsengs from different sources were determined simultaneously. The ratio of the total content of determined malonyl ginsenosides to the corresponding neutral ginsenosides (T(m-PPD)/T(PPD)) in white ginseng ranged from 0.46 to 0.62 and from 0 to 0.19 in red ginseng. The validated method is expected to provide an effective approach to standardize the processing procedures of ginseng products and regulate the usage of ginseng in Traditional Chinese Medical prescription.

Cost-effectiveness analysis of colorectal cancer screening with stool DNA testing in intermediate-incidence countries.

BACKGROUND: The aim of this study is to compare the cost-effectiveness of screening with stool DNA testing with that of screening with other tools (annual fecal occult blood testing, flexible sigmoidoscopy every 5 years, and colonoscopy every 10 years) or not screening at all. METHODS: We developed a Markov model to evaluate the above screening strategies in the general population 50 to 75 years of age in Taiwan. Sensitivity analyses were performed to assess the influence of various parameters on the cost-effectiveness of screening. A third-party payer perspective was adopted and the cost of dollar 13,000 per life-year saved (which is roughly the per capita GNP of Taiwan in 2003) was chosen as the ceiling ratio for assessing whether the program is cost-effective. RESULTS: Stool DNA testing every three, five, and ten years can reduce colorectal cancer mortality by 22%, 15%, and 9%, respectively. The associated incremental costs were dollar 9,794, dollar 9,335, and dollar 7,717, per life-year saved when compared with no screening. Stool DNA testing strategies were the least cost-effective with the cost per stool DNA test, referral rate with diagnostic colonoscopy, prevalence of large adenoma, and discount rate being the most influential parameters. CONCLUSION: In countries with a low or intermediate incidence of colorectal cancer, stool DNA testing is less cost-effective than the other currently recommended strategies for population-based screening, particularly targeting at asymptomatic subjects.