Unravelling the health and economic burden of interstitial lung diseases in adults in Australia.

BACKGROUND: Interstitial lung diseases (ILD) are a heterogenous group of over 200 disorders affecting the pulmonary interstitium. Although there have been advances in knowledge on ILDs in Australia, the characterisation of the health and economic burden of disease remained largely undetermined until recently. OBJECTIVE: The main objective of this review is to provide a synopsis of health and economic burden of ILDs in Australia, based on recently completed research. DISCUSSION: Recent research has demonstrated that idiopathic pulmonary fibrosis (IPF) is the most frequent ILD in Australia. Incidence and prevalence of IPF have demonstrated an increasing trend over the past decades. Mortality has also increased over the past decades, but has shown a slight decreasing trend recently, since the introduction of antifibrotic medication. Health-related quality of life is poor in patients with IPF, and care is estimated to cost approximately AU$299 million per year in Australia. Early diagnosis and referral to tertiary care is crucial for favourable outcomes, and general practitioners are considerably important to this as the first interface to identify patients at risk and detect early symptoms of ILDs.

Development of an Interpretable Deep Learning Model for Pathological Tumor Response Assessment After Neoadjuvant Therapy.

BACKGROUND: Neoadjuvant therapy followed by surgery has become the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC) and accurate pathological response assessment is critical to assess the therapeutic efficacy. However, it can be laborious and inconsistency between different observers may occur. Hence, we aim to develop an interpretable deep-learning model for efficient pathological response assessment following neoadjuvant therapy in ESCC. METHODS: This retrospective study analyzed 337 ESCC resection specimens from 2020-2021 at the Pudong-Branch (Cohort 1) and 114 from 2021-2022 at the Puxi-Branch (External Cohort 2) of Fudan University Shanghai Cancer Center. Whole slide images (WSIs) from these two cohorts were generated using different scanning machines to test the ability of the model in handling color variations. Four pathologists independently assessed the pathological response. The senior pathologists annotated tumor beds and residual tumor percentages on WSIs to determine consensus labels. Furthermore, 1850 image patches were randomly extracted from Cohort 1 WSIs and binarily classified for tumor viability. A deep-learning model employing knowledge distillation was developed to automatically classify positive patches for each WSI and estimate the viable residual tumor percentages. Spatial heatmaps were output for model explanations and visualizations. RESULTS: The approach achieved high concordance with pathologist consensus, with an R^2 of 0.8437, a RAcc_0.1 of 0.7586, a RAcc_0.3 of 0.9885, which were comparable to two senior pathologists (R^2 of 0.9202/0.9619, RAcc_0.1 of 8506/0.9425, RAcc_0.3 of 1.000/1.000) and surpassing two junior pathologists (R^2 of 0.5592/0.5474, RAcc_0.1 of 0.5287/0.5287, RAcc_0.3 of 0.9080/0.9310). Visualizations enabled the localization of residual viable tumor to augment microscopic assessment. CONCLUSION: This work illustrates deep learning's potential for assisting pathological response assessment. Spatial heatmaps and patch examples provide intuitive explanations of model predictions, engendering clinical trust and adoption (Code and data will be available at https://github.com/WinnieLaugh/ESCC_Percentage once the paper has been conditionally accepted). Integrating interpretable computational pathology could help enhance the efficiency and consistency of tumor response assessment and empower precise oncology treatment decisions.

Network pharmacology‒based analysis of marine cyanobacteria derived bioactive compounds for application to Alzheimer's disease.

In recent years, the Alzheimer's disease (AD) epidemic has become one of the largest global healthcare crises. Besides, the available systemic therapies for AD are still inadequate. Due to the insufficient therapeutic options, new treatment strategies are urgently needed to achieve a satisfactory therapeutic effect. Marine bio-resources have been accepted as one of the most economically viable and sustainable sources with potential applications for drug discovery and development. In this study, a marine cyanobacteria-Synechococcus sp. XM-24 was selected as the object of research, to systematically investigate its therapeutic potential mechanisms for AD. The major active compounds derived from the Synechococcus sp. biomass were identified via pyrolysis-gas chromatography-mass spectrometry (GC-MS), and 22 compounds were identified in this strain. The most abundant chemical compounds was (E)-octadec-11-enoic acid, with the peak area of 30.6%. Follow by tridecanoic acid, 12-methyl- and hexadecanoic acid, with a peak area of 23.26% and 18.23%, respectively. GC-MS analysis also identified indolizine, isoquinoline, 3,4-dihydro- and Phthalazine, 1-methyl-, as well as alkene and alkane from the strain. After the chemical toxicity test, 10 compounds were finally collected to do the further analysis. Then, network pharmacology and molecular docking were adopted to systematically study the potential anti-AD mechanism of these compounds. Based on the analysis, the 10 Synechococcus-derived active compounds could interact with 128 related anti-AD targets. Among them, epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA) and mitogen-activated protein kinase 3 (MAPK3) were the major targets. Furthermore, the compounds N-capric acid isopropyl ester, (E)-octadec-11-enoic acid, and 2H-Pyran-2,4(3H)-dione, dihydro-6-methyl- obtained higher degrees in the compounds-intersection targets network analysis, indicating these compounds may play more important role in the process of anti-AD. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that these active compounds exert the anti-AD effects mainly through PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction and ras signaling pathway. Our study identified Synechococcus-derived bioactive compounds have the potential for application to AD by targeting multiple targets and related pathways, which will provide a foundation for future research on applications of marine cyanobacteria in the functional drug industry.

A Cost-effectiveness Analysis of iGlarLixi Versus IDegAsp and Appropriate Price Exploration of iGlarLixi for Type 2 Diabetes Mellitus Patients in China.

BACKGROUND AND OBJECTIVE: The efficacy and safety of iGlarLixi, a fixed-ratio combination (FRC) of basal insulin glargine plus lixisenatide, have been demonstrated in type 2 diabetes mellitus (T2DM) patients. However, no relevant economic analysis of iGlarLixi has been done in China. Thus, the primary objective of this study is to evaluate the cost effectiveness of iGlarLixi versus IDegAsp in Chinese T2DM patients, and then back-calculate the appropriate drug price of iGlarLixi to support its pricing after listing in China. METHODS: The United Kingdom Prospective Diabetes Study Outcome Model 2 (UKPDS OM2) was applied to estimate lifetime health and economic outcomes from the Chinese health-care system perspective. As no head-to-head comparison data are currently available, the baseline cohort characteristics and the initial clinical data for iGlarLixi were derived from the randomized LixiLan-L-China trial. The relative treatment effects for IDegAsp were based on an indirect treatment comparison. Due to the unavailability of iGlarLixi pricing data, the annual medication cost of iGlarLixi was assumed to be equal to that of IDegAsp at the beginning of the study. Afterwards, a break-even analysis using comparator drug price and the willingness-to-pay (WTP) threshold was performed to back-calculate the appropriate drug price of iGlarLixi. One-way sensitivity analysis, scenario analysis and probabilistic sensitivity analysis (PSA) were conducted to assess the robustness of the model. RESULTS: Based on the initial assumption of equal annual medication cost of iGlarLixi and IDegAsp, iGlarLixi was cost effective compared to IDegAsp with an incremental cost-effectiveness ratio (ICER) far below the WTP threshold in Chinese T2DM patients. From the back calculation for the price of iGlarLixi, the annual medication cost of iGlarLixi was $656.96 and $1075.96 to obtain an ICER of iGlarLixi versus IDegAsp close to 1 × GDP and 3 × GDP, respectively. When the discount rate was changed from the base value to 8% (the most sensitive parameter to the model results in one-way sensitivity analysis), the ICER was nearly equal to 1 × GDP and 3 × GDP with the annual medication cost of iGlarLixi decreasing to $590.41 and $865.03, respectively. Thus, iGlarLixi was dominant over IDegAsp with an annual medication cost of $590.41 to $865.03. The findings were robust to one-way sensitivity analysis, PSA and scenario analysis. CONCLUSION: This long-term cost-effectiveness analysis in Chinese T2DM patients indicates that iGlarLixi, assuming equal price to IDegAsp, is cost-effective versus IDegAsp with an ICER far below the WTP threshold. With 1 × GDP and 3 × GDP threshold set we back-calculate the appropriate annual medication cost of iGlarLixi to be $590.41 to $865.03, respectively.

Automated measurement of leg length discrepancy from infancy to adolescence based on cascaded LLDNet and comprehensive assessment.

Background: Deep learning (DL) has been suggested for the automated measurement of leg length discrepancy (LLD) on radiographs, which could free up time for pediatric radiologists to focus on value-adding duties. The purpose of our study was to develop a unified solution using DL for both automated LLD measurements and comprehensive assessments in a large and comprehensive radiographic dataset covering children at all stages, from infancy to adolescence, and with a wide range of diagnoses. Methods: The bilateral femurs and tibias were segmented by a cascaded convolutional neural network (CNN), referred to as LLDNet. Each LLDNet was conducted through use of residual blocks to learn more abundant features, a residual convolutional block attention module (Res-CBAM) to integrate both spatial and channel attention mechanisms, and an attention gate structure to alleviate the semantic gap. The leg length was calculated by localizing anatomical landmarks and computing the distances between them. A comprehensive assessment based on 9 indices (5 similarity indices and 4 stability indices) and the paired Wilcoxon signed-rank test was undertaken to demonstrate the superiority of the cascaded LLDNet for segmenting pediatric legs through comparison with alternative DL models, including ResUNet, TransUNet, and the single LLDNet. Furthermore, the consistency between the ground truth and the DL-calculated measurements of leg length was also comprehensively evaluated, based on 5 indices and a Bland-Altman analysis. The sensitivity and specificity of LLD >5 mm were also calculated. Results: A total of 976 children were identified (0-19 years old; male/female 522/454; 520 children between 0 and 2 years, 456 children older than 2 years, 4 children excluded). Experiments demonstrated that the proposed cascaded LLDNet achieved the best pediatric leg segmentation in both similarity indices (0.5-1% increase; P<0.05) and stability indices (13-47% percentage decrease; P<0.05) compared with the alternative DL methods. A high consistency of LLD measurements between DL and the ground truth was also observed using Bland-Altman analysis [Pearson correlation coefficient (PCC) =0.94; mean bias =0.003 cm]. The sensitivity and specificity established for LLD >5 mm were 0.792 and 0.962, respectively, while those for LLD >10 mm were 0.938 and 0.992, respectively. Conclusions: The cascaded LLDNet was able to achieve promising pediatric leg segmentation and LLD measurement on radiography. A comprehensive assessment in terms of similarity, stability, and measurement consistency is essential in computer-aided LLD measurement of pediatric patients.

The relative contribution of co-morbidities to health-related quality of life of people with idiopathic pulmonary fibrosis using the Assessment of Quality of Life-8-Dimension multi-attribute utility instrument.

PURPOSE: Little is known about the impact of co-morbidities on health-related quality of life (HRQoL) for people with idiopathic pulmonary fibrosis (IPF). We aimed to investigate the relative contribution of co-morbidities to HRQoL of people with IPF. METHODS: N = 157 participants were recruited from the Australian IPF Registry (AIPFR). Health state utilities (HSUs), and the super-dimensions of physical and psychosocial scores were measured using the Assessment of Quality of Life-8-Dimensions (AQoL-8D). The impact of co-morbidities on HRQoL was investigated using linear regression and general dominance analyses. RESULTS: A higher number of co-morbidities was associated with lower HSUs (p trend = 0.002). Co-morbidities explained 9.1% of the variance of HSUs, 16.0% of physical super-dimensional scores, and 4.2% of psychosocial super-dimensional scores. Arthritis was associated with a significant reduction on HSUs (ß = - 0.09, 95% confidence interval [CI] - 0.16 to - 0.02), largely driven by reduced scores on the physical super-dimension (ß = - 0.13, 95% CI - 0.20 to - 0.06). Heart diseases were associated with a significant reduction on HSUs (ß = - 0.09, 95% CI - 0.16 to - 0.02), driven by reduced scores on physical (ß = - 0.09, 95% CI - 0.16 to - 0.02) and psychosocial (ß = -0.10, 95% CI - 0.17 to - 0.02) super-dimensions. CONCLUSIONS: Co-morbidities significantly impact HRQoL of people with IPF, with markedly negative impacts on their HSUs and physical health. A more holistic approach to the care of people with IPF is important as better management of these co-morbidities could lead to improved HRQoL in people with IPF.

Assessment of the influence on left ventricle by potassium oxonate and hypoxanthine-induced chronic hyperuricemia.

Cellular cytoplasmic xanthine oxidase (XO)-mediated uric acid synthesis and extracellular excess uric acid exposure are both causes of cardiomyocytic injury under the condition of hyperuricemia (HUA). Potassium oxonate suppresses uric acid degradation to increase extracellular concentration, while hypoxanthine is the catalytic substrate of XO. We aimed to observe cardiac damage in a chronic HUA mouse model induced by potassium oxonate and hypoxanthine. The mouse model was established by the co-administration of potassium oxonate and hypoxanthine for eight weeks. Then, left ventricular parameters were examined by echocardiographic evaluation, and the heart tissues were harvested for further histopathological analysis. The results showed that plasma uric acid was persistently elevated in the model mice, which demonstrated the stable establishment of chronic HUA. The left ventricular anterior wall was significantly thickened in the model group compared with the blank control group. After the end of modeling, the left ventricular anterior wall thickness of the hyperuricemic mice increased compared with that of blank group. The histological analysis showed and myocardial structure disorganization in the model group compared with the blank control. The above cardiac impairment changes could be attenuated by allopurinol pretreatment. This study systematically assessed cardiac damage in a chronic HUA mouse model. In addition, it provides useful information for future HUA-associated heart injury mechanism investigation and therapeutic treatment evaluation.

Thermo-soil weathering and life cycle assessment of carbon black, silica and cellulose nanocrystal filled rubber nanocomposites.

Carbon black (CB) and silica (Sil) as rubber reinforcement have raised environmental concerns for being high resources consumptive and less susceptible towards biodegradability. Cellulose nanocrystal (CNC) has demonstrated great potentials for use as biodegradable nanofillers in rubber nanocomposites while evaluation of its environmental impacts with optimal end-of-life (EOL) choices is not carried out. To simulate realistic EOL, thermo-oxidative aging and soil burial aging behaviors of rubber nanocomposites with 33.3% filler were performed. The environmental weathering performance modeled with the help of life cycle assessment (LCA) illustrates increased biodegradation susceptibility with partial replacement of CB or Sil with CNC in the nanocomposites, hence promoting the environmental solutions for waste minimalization by enhancing the biodegradability potentials. In terms of LCA, the CNC incorporation contributes more to the environmental impacts in manufacturing but greatly lowers the EOL choices, by reducing the global warming potential values.

Stretchable, Self-Healing, and Skin-Mounted Active Sensor for Multipoint Muscle Function Assessment.

Assessment of muscle function is an essential indicator for estimating elderly health, evaluating motor function, and instructing rehabilitation training, which also sets urgent requirements for mechanical sensors with superior quantification, accuracy, and reliability. To overcome the rigidity and vulnerability of traditional metallic electrodes, we synthesize an ionic hydrogel with large deformation tolerance and fast self-healing ability. And we propose a stretchable, self-healing, and skin-mounted (Triple S) active sensor (TSAS) based on the principles of electrostatic induction and electrostatic coupling. The skin modulus-matched TSAS provides outstanding sensing properties: maximum output voltage of 78.44 V, minimal detection limit of 0.2 mN, fast response time of 1.03 ms, high signal-to-noise ratio and excellent long-term service stability. In training of arm muscle, the functional signals of biceps and triceps brachii muscles as well as the joint dexterity of bending angle can be acquired simultaneously through TSAS. The signal can also be sent wirelessly to a terminal for analysis. With the characteristics of high sensitivity, reliability, convenience, and low-cost, TSAS shows its potential to be the next-generation procedure for real-time assessment of muscle function and rehabilitation training.

Cost of Blood and Body Fluid Occupational Exposure Management in Beijing, China.

(1) Objective: The aim of this study was to determine the cost of blood and body fluid (BBF) occupational exposure management in healthcare facilities in Beijing, China. (2) Methods: A survey was conducted from August to October 2018, seeking general information concerning the management of occupational exposure to BBF and the cost of the management process. In total, 216 healthcare facilities were surveyed, using a stratified-selection method. The collected information included BBF management protocols, direct costs such as laboratory testing fees, drug costs and medical service fees, as well as indirect costs, such as wages, lost working time, injury compensation, and psychological counseling time. (3) Results: The cost of post-BBF exposure management varied according to the infection status of the exposure source patients, the immune status of exposed employees, and the location and level of healthcare facilities. The mean values of management cost were determined to be hepatitis B (HBV)-positive source (RMB 5936/USD 897), hepatitis C (HCV)-positive source (RMB 5738/USD 867), Treponema pallidum (TP)-positive source (RMB 4508/USD 681), human immunodeficiency virus (HIV)-positive source (RMB 12,709/USD 1920), and unknown sources (RMB 7441/USD 1124). The survey also revealed that some healthcare facilities have insufficient post-exposure management. (4) Conclusions: A better post-exposure management system is needed in Beijing to reduce both infection risk after exposure and costs.

Co-pretreatment of wheat straw by potassium hydroxide and calcium hydroxide: Methane production, economics, and energy potential analysis.

To improve the methane production of wheat straw (WS), the mono-pretreatment (MP) and co-pretreatment (CP) of WS with KOH and Ca(OH)2 were conducted in this study. The results showed that the MP with KOH presented better effects than the MP with Ca(OH)2. However, the CP with 2% KOH combined with 1% Ca(OH)2 displayed similar effects to those of the MP with 3% KOH, obtaining the cumulative methane yield of 239.8 mL gVS-1 and an improved biodegradability from 56.37% of raw WS to 66.10%. Methane production and kinetic analyses suggested that 2% KOH combined with 1% Ca(OH)2 was the ideal condition of alkaline pretreatment for anaerobic digestion of WS. The mechanism for the improvement in methane production was clearly described by biochemical component, scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analyses. Moreover, preliminary economics and energy potential analyses also confirmed that alkaline co-pretreatment was a reasonable method, which not only gave important guidance for future utilization of WS waste but also showed useful reference for the efficient pretreatment of other lignocellulosic wastes.

Economic Impacts of the Generic Drug User Fee Act Fee Structure.

BACKGROUND: A Food and Drug Administration (FDA) Generic Drug User system, Generic Drug User Fee Amendment of 2012 (GDUFA), started October 1, 2012, and has been in place for over 3 years. There is controversy about the GDUFA fee structure but no analysis of GDUFA data that we could find. OBJECTIVE: To look at the economic impact of the GDUFA fee structure. METHODS: We compared the structure of GDUFA with that of other FDA Human Drug User fees. We then, using FDA-published information, analyzed where GDUFA facility and Drug Master File fees are coming from. We used the Orange Book to identify the sponsors of all approved Abbreviated New Drug Applications (ANDAs) and the S&P Capital IQ database to find the ultimate parent companies of sponsors of approved ANDAs. RESULTS: The key differences between the previous structure for Human Drug User fees and the GDUFA are as follows: GDUFA has no approved product fee and no first-time or small business fee exemptions and GDUFA charges facility fees from the time of filing and charges a foreign facility levy. Most GDUFA fees are paid by or on behalf of foreign entities. The top 10 companies hold nearly 50% of all approved ANDAs but pay about 14% of GDUFA facility fees. CONCLUSIONS: We conclude that the regressive nature of the GDUFA fee structure penalizes small, new, and foreign firms while benefiting the large established firms. A progressive fee structure in line with other human drug user fees is needed to ensure a healthy generic drug industry.

Early assessment of coagulation necrosis after hepatic microwave ablation: a comparison of non-enhanced and enhanced T1-weighted images.

PURPOSE: To compare the technical success and accuracy of hepatic microwave ablation (MWA) using non-enhanced and enhanced T1-weighted imaging early after ablation. Patients were evaluated with regard to the ablation zone and local tumor progression (LTP). METHODS: This retrospective study conducted between September 2014 and December 2015 which consisted of 56 patients with 56 hepatic malignant lesions who underwent percutaneous MWA. Non-enhanced and contrast-enhanced T1-weighted imagings were performed within 2 days after tumor ablation. The efficacy of ablation assessed according to the hyperintense middle zone on non-enhanced T1-weighted images and the non-enhanced area on contrast-enhanced T1-weighted images were compared. The development of LTP during ≥7 months of follow-up served as the end point. RESULTS: On the non-enhanced T1-weighted images, the ablated region had a characteristic two-zone structure featuring a hyperintense middle zone and a surrounding hypointense band. Among the 56 patients, LTP developed in ten including seven lesions, in which both the non-enhanced T1-weighted and portal-phase images showed incomplete tumor ablation. In two of the remaining three patients, incomplete tumor ablation was detected on the non-enhanced T1-weighted images, whereas the corresponding portal-phase images showed complete ablation. In the remaining patient, no residual tumor was detected on either the non-enhanced T1-weighted or the portal-phase images. In the 46 patients without LTP, there was no evidence of residual tumor on the non-enhanced T1-weighted or portal-phase images obtained early after ablation. CONCLUSIONS: Non-enhanced T1-weighted images are useful in assessing the therapeutic efficacy of MWA of liver tumors early after the procedure.

Medicaid-insured and uninsured were more likely to have diabetes emergency/urgent admissions.

OBJECTIVES: To evaluate the associations between potentially avoidable diabetes-related emergency/urgent hospital admissions and different health insurance status (ie, Medicaid, Medicare, uninsured, private), along with other characteristics including sociodemographic status (age, race/ethnicity, gender, region), hospitalization status (previous hospitalizations, weekend admissions), and health status (complications, comorbidities), among patients with type 2 diabetes mellitus (T2DM). STUDY DESIGN: The 2011 data set of all inpatient discharge records with a primary diagnosis of T2DM from all hospitals in Pennsylvania were included in the analyses. METHODS: Multivariable logistic regression modeling with diabetes-related emergency/urgent hospitalizations as the dependent outcome variable and health insurance status as the main exposure independent variable, adjusting for age, race/ethnicity, gender, region, previous hospitalizations, weekend admissions, complications, and comorbidity. Hosmer and Lemeshow goodness-of-fit test was used for logistic model fit analysis. RESULTS: Nearly 91% of 17,097 potentially avoidable diabetes-related hospitalizations were emergency/urgent admissions for T2DM patients in Pennsylvania during 2011. Uninsured and Medicaidinsured patients were 2.1 (adjusted odds ratio [AOR], 2.11; 95% CI, 1.23-3.61) and 1.8 (AOR, 1.78; 95% CI, 1.44-2.20) times more likely than privately insured patients, respectively, to be admitted through emergency/urgent admissions. There was no statistically significant difference in emergency/urgent admissions between Medicaid and uninsured (AOR, 0.85; 95% CI, 0.49-1.47). CONCLUSIONS: Medicaid-insured T2DM patients, like the uninsured, are more likely to be hospitalized through emergency/urgent admissions. The presumption that insured individuals with diabetes are more likely than the uninsured to manage and control the progression of their condition, and receive care in the right setting, is not supported for those with Medicaid coverage.

[Cell-free protein synthetic system: progress and applications in biopharmaceutical engineering].

Cell-free protein synthesis (CFPS) systems based on crude cell extracts have been used in protein expression in vitro. With the researchers' endeavor for decades, the CFPS system has been developed as an important research tool in many frontiers of fundamental and applied biology because of its clear genetic background and simplicity to control the reaction. The yield of CFPS systems derived from prokaryote or eukaryote has increased to several grams per liter with constantly decreasing cost. Nowadays grams of protein could be prepared using a large-scale cell-free system. Recently, the advantages on the expression of complicated, toxic and membrane proteins have shown the great potential of the CFPS systems. The rapid progress of this technology made us to believe that it will take an important place in biopharmaceutical industries undoubtedly.

[Application and benefit evaluation of tiered health risk assessment approach on site contaminated by benzene].

The procedures of implementing tiered health risk assessment approach were introduced in detail, and took a large-scale site polluted by benzene in Beijing as an example, the difference on the remediation target of benzene in soil, as well as the corresponding soil remediation volume and costs, were compared. The results indicate that the benzene concentration in soil within 1.5 m in depth and the one below should be remediated to 0.26 mg x kg(-1) and 0.15 mg x kg(-1), respectively, in order to keep the cumulative carcinogenic health risk below 1 x 10(-6) based on tiered II assessment. However, according to tiered III assessment result, which is based on the benzene in soil gas within the contaminated areas in the investigated site, the soil in the corresponding depth should only be remediated to 2.6 mg x kg(-1) and 1.5 mg x kg(-1), respectively. That means the soil remediation volume delimited on tiered III assessment result is less than the one on tiered II by 139 537 m3 and the corresponding remediation costs will be reduced by 57 million Yuan, meaning the enormous economic benefits compared to the costs (around 100 thousands Yuan) spent to carry out tiered III assessment in the site.

Evidence-based decision-making on medical technologies in China, Japan, and Singapore.

OBJECTIVE: To review the use of evidence in the market approval process, reimbursement, and price control mechanisms for medicines and medical devices in China, Japan, and Singapore. METHODOLOGY: Documentary reviews relevant to public health policy and management by government authorities. RESULTS: Drug regulatory authorities play a vital role in the market authorization process of medical technologies. The approval criteria in the three countries are similar to those of the US Food and Drug Administration and many other countries, whose core measures are efficacy, safety, and quality, along with risk-based analyses in China and Singapore. All established the national drug list (Japan) or lists (China and Singapore) for reimbursement. Although Japan reimburses any drugs listed, China and Singapore selectively reimburse regarding the types of the list. The cost-effectiveness is utilized for prioritization of new drugs listed in Singapore. Japan controls the price by government, whereas Singapore keeps market liberalism, and China maintains a mixture of both. CONCLUSION: All three countries have established their own mechanisms, but cost-effectiveness requirements have not been fully introduced yet, partially applied to the reimbursement processes in Singapore.