Effect of air pollution on health care expenditure: Evidence from respiratory diseases.

Recent reports show that at least 95% of the world's population is breathing polluted air. However, the impact of air quality on air pollution-related medical expenditure and utilization is sparse. This study estimates the short-term health care cost impacts of air pollution using a meteorological phenomenon-thermal inversion-as an instrumental variable for air quality. Using information on outpatient care for respiratory diseases from universal health insurance claim data in Taiwan during 2006-2012, our estimates suggest that a one-unit reduction in the air quality index (AQI) leads to NT$2.3 billion (nearly US$74 million) of savings in respiratory-related outpatient expenditure per year. Given that the average AQI is equal to 32 during our study period, completely removing air pollution would reduce the national health expenditure by approximately 8% annually. Our results provide the important implication that the cost of controlling air pollutant emissions can be offset by curtailing health care expenditure.

[Synergistic Effect of 2-deoxy-D-glucose Combined with Hydroxycamptothecin on Apoptosis of Breast Cancer Cells].

OBJECTIVE: To investigate the effect of 2-deoxy-d-glucose (2-DG) combined with hydroxycamptothecin (HCPT) on anti-tumor activity of breast cancer cells and its mechanism. METHODS: MDA-MB-231 and MCF-7 breast cancer cells were incubated with varying concentrations of 2-DG (0, 1.25, 2.5, 5, 10, 20 mmol/L), HCPT(0, 5, 10, 20, 40 µmol/L) and 2-DG (5 mmol/L) combined with HCPT. Cell viability was measured using the MTT assay; Propidium iodide (PI) detected the apoptosis of MDA-MB-231 cells by 5 mmol/L 2-DG, 10 µmol/L HCPT alone or in combination; MDA-MB-231 cells were treated with 2-DG (0, 2.5, 5, 10, 20 mmol/L) and the level of ATP was detected by ATP kit; the expression of Akt, p-Akt, Bcl-2/Bax, PARP, Caspase-8 and Caspase-3 proteins in MDA-MB-231 cells were measured by Western blot assay. RESULTS: The combination of 2-DG (5 mmol/L) and HCPT had a synergistic effect. The 48 h combination index (CI < 1) was higher than that of the single-use group (P < 0.05). At the same time, the combination of the two drugs inhibits the phosphorylation of Akt protein and increases the activation of Caspase-3 protein, thereby increasing the cleavage of PARP proteins. CONCLUSION: The combination of 2-DG and HCPT can synergistically induce the apoptosis of breast cancer cells, which may be caused by inhibiting the energy generation of tumor cells, inhibiting the phosphorylation of Akt protein and enhancing the activity of caspase-3 protein.

Down-Regulation of Laminin (LN)- α5 is Associated with Preeclampsia and Impairs Trophoblast Cell Viability and Invasiveness Through PI3K Signaling Pathway.

BACKGROUND/AIMS: Preeclampsia (PE) is a gestational disorder defined as hypertension and proteinuria, which is deemed a major cause of maternal and neonatal mortality and morbidity worldwide. The aim of this study was to investigate the expression patterns of placental laminin (LN)-α5 expression in normal and PE pregnancies, as well as evaluating the effects of LN-α5 on trophoblast proliferation, apoptosis, and invasion. METHODS: LN-α5 expression levels were examined by reverse-transcriptase polymerase chain reaction (RT-PCR), and further confirmed by western blotting and immunofluorescence staining. Cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry. Cell invasion was assessed by matrigel-based transwell assay. LN-α5 DNA methylation in placentas was determined by bisulfite sequencing PCR (BSP). RESULTS: LN-α5 expression levels in PE placentas were significantly lower than that of normal pregnancies. Deficiency in LN-α5 expression resulted in decreased trophoblast proliferation and invasion but increased cell apoptosis, meanwhile, PI3K/AKT/mTOR signaling pathway was impaired by LN-α5 silencing. LN-α5 promoter methylation didn't show significant difference between PE and normal placentas. CONCLUSION: LN-α5 downregulation is associated with PE placenta and impairs trophoblast viability and invasiveness, which could be a causative factor of PE pathogenesis.

[Effect of SRC Kinase on Adriamycin Resistance and Invasion and Metastasis in Human Breast Cancer Cells].

OBJECTIVE: To investigate the role of SRC kinase inhibitor PP2 in drug resistance to adriamycin (ADM) in breast cancer cells and invasion, metastasis of cells. METHODS: MTT assay was used to detect the inhibitory effect of ADM on MCF-7 and MCF-7/ADM cells. The 50% inhibitory concentration (IC50) and resistance index (RI) of cells were calculated. The expression of MDR1, connexin 43 (Cx43) and SRC proteins in breast cancer cells were detected by Western blot assay. Transwell experiment and cell scratch test were used to determine the invasion and migration of cells respectively [MCF-7, MCF-7/ADM, PP2 (1, 2, 4 µmol/L)]. Standard colony formation assay was used to detect the cytotoxicity effect of 4 µmol/L PP2 pretreatment on ADM. RESULTS: ADM inhibited the proliferation of MCF-7 more than MCF-7/ADM cells (P<0.01). The IC50 of MCF-7/ADM cells was 24.55 µmol/L, the IC50 of MCF-7/ADM cells was 770.57 µmol/L, the RI was 31. Compared with MCF-7 cells, expressions of the multidrug resistance proteins MDR1 and SRC were significantly increased (P<0.01). The invasion and migration ability of the MCF-7/ADM cells was stronger than that of the sensitive cells (P<0.01). When MCF-7/ADM was exposed to SRC inhibitor PP2, the invasion and metastasis ability of cells were inhibited (P<0.01) and the rate of colony formation was decreased, that is, more sensitivity to ADM (P<0.01). CONCLUSION: The resistance of MCF-7 to ADM is accompanied by increased expression of SRC. SRC inhibitor PP2 can reduce the cell resistance, ability of invasion and metastasis.

Exploring the relationship between nursing hours per patient day and mortality rate of hospitalised patients in Taiwan.

AIM: To investigate the relationship between nursing hours per patient day and the inpatient mortality rate in Taiwan. BACKGROUND: Nursing hours per patient day has been associated with better patient outcomes. The literature is inconclusive on the relationship between nursing hours per patient day and the inpatient mortality rate, and no studies have yet examined this issue in Taiwan. METHODS: A retrospective longitudinal study analysed data from the 'Nursing Utilization of Resources, Staffing and Environment on Outcome Study: NURSE-outcome study'. Hierarchical regression estimated the relationship between nursing hours per patient day and in-hospital mortality rate after controlling for confounding variables. RESULTS: The mean nursing hours per patient day in Taiwan was 2.3, while the mean inpatient mortality rate was 0.73% higher nursing hours per patient day was associated with a lower inpatient mortality rate after controlling for confounding variables. The total explained variance of this study in inpatient mortality rate was 19.9%. Significant relationships to inpatient mortality were found in levels of hospitals, seasonal variation and nurses' work experience. CONCLUSION: Nursing hours per patient day affects the mortality rate among hospitalised patients in Taiwan. IMPLICATIONS FOR NURSING MANAGEMENT: According to the results, we suggested the government and managers in Taiwan double the nursing hours per patient day so that the inpatient mortality rate will decline by 1.1%. This might be the optimal nurse configuration that could provide a balance between cost-effectiveness and patient safety.

High expression of beta2-glycoprotein I is associated significantly with the earliest stages of hepatitis B virus infection.

Human beta2-glycoprotein I (beta2-GPI) binds to recombinant hepatitis B surface antigen (rHBsAg) and can bind specifically to annexin II, which is located on the cell membrane of human hepatoma SMMC-7721 cells. Viral envelope proteins are essential for mediating cellular entry. The aim of this study was to investigate the role of beta2-GPI in the early stages of hepatitis B virus (HBV) infection. Western blot and qRT-PCR analyses revealed that beta2-GPI expression was upregulated in HepG2.2.15 cells at both the mRNA and protein level and was almost non-existent in 293T and CHO cells. Furthermore, annexin II was expressed at lower levels in HepG2.2.15 cells compared to L02, HepG2, and SMMC-7721 cells. Additionally, ELISA analyses demonstrated that beta2-GPI enhanced the ability of HBsAg to bind to cell surfaces, and there was differential adhesion to L02, HepG2, HepG2.2.15, and 293T cells. Western blot and ELISA were then performed to assess the effects of HBV and the HBsAg domain on beta2-GPI expression in co-transfected 293T cells. This study revealed that HBV and the large HBV envelope protein increased beta2-GPI expression. Further investigation indicated that beta2-GPI colocalized with HBsAg in the cytosol of HepG2.2.15 cells, with sodium taurocholate co-transporting polypeptide (NTCP) on the cell membrane in NTCP-complemented HepG2 cells, and with annexin II in the cytosol of HepG2 and HepG2.2.15 cells. These data suggest that high expression of beta2-GPI enhances HBsAg binding to cell surfaces, thus contributing to virus particle transfer to the NTCP receptor and interaction with annexin II for viral membrane fusion.

Turn-on phosphorescent chemodosimeter for Hg2+ based on a cyclometalated Ir(III) complex and its application in time-resolved luminescence assays and live cell imaging.

A novel "turn-on" phosphorescent chemodosimeter based on a cyclometalated Ir(III) complex has been designed and synthesized, which displays high selectivity and sensitivity toward Hg(2+) in aqueous media with a broad pH range of 4-10. Furthermore, by time-resolved photoluminescence techniques, some interferences from the short-lived background fluorescence can be eliminated effectively and the signal-to-noise ratio of the emission detection can be improved distinctly by using the chemodosimeter. Finally, the chemodosimeter can be used to monitor Hg(2+) effectively in living cells by confocal luminescence imaging.

Choice of generic versus brand-name antidepressants in a regulated prescription drug market: evidence from Taiwan.

BACKGROUND: A health care system in which there is no separation between prescription and dispensation, combined with a regulated prescription drug market, leads to various generic substitution mechanisms for antidepressants. AIMS OF THE STUDY: We investigated the determinants of generic versus brand-name antidepressant choices in a regulated prescription market where physicians both prescribe and dispense drugs. METHODS: Using data from a sample of one million individuals selected randomly from the registry of National Health Insurance beneficiaries in 2010, and all claims for these one million enrollees between January 1997 and December 2011, we employed logistic regression to examine the choice of generic versus brand-name antidepressants in the Taiwanese prescription drug market. RESULTS: Access to various antidepressant brands varies according to the accreditation level and type of ownership of the healthcare provider. Private healthcare providers and those with lower accreditation levels were more likely to prescribe generic antidepressants compared to their brand-name counterparts. The diversity of products and competition in the molecule market was positively associated with the probability of prescribing generic antidepressants. DISCUSSION: In a regulated prescription drug market with no separation between prescription and dispensation, the substitution of generic antidepressant prescriptions in place of brand-name prescriptions is likely driven by drug and provider market characteristics, rather than by lowering costs. IMPLICATIONS FOR HEALTHCARE PROVISION: The allocation of different types of ownership and accreditation levels of healthcare providers may lead to unequal access to various brands of antidepressants. IMPLICATIONS FOR HEALTH POLICIES: Policies for improving the treatment of depression should take into account the structure of molecule and provider markets as important factors in determining the choice and utilization of antidepressants, in a healthcare system where physicians both prescribe and dispense drugs. IMPLICATIONS FOR FUTURE RESEARCH: Other psychotropic drug classes should be investigated to explore the effect of molecule and provider characteristics on the utilization of various classes of medication.

Identification of lung adenocarcinoma subtypes and a prognostic signature based on activity changes of the hallmark and immunologic gene sets.

Background: Lung adenocarcinoma (LUAD) has a complex tumor heterogeneity. Our research attempts to clearness LUAD subtypes and build a reliable prognostic signature according to the activity changes of the hallmark and immunologic gene sets. Methods: According to The Cancer Genome Atlas (TCGA) - LUAD dataset, changes in marker and immune gene activity were analyzed, followed by identification of prognosis-related differential gene sets (DGSs) and their related LUAD subtypes. Survival analysis, correlation with clinical characteristics, and immune microenvironment assessment for subtypes were performed. Moreover, the differentially expressed genes (DEGs) between different subtypes were identified, followed by the construction of a prognostic risk score (RS) model and nomogram model. The tumor mutation burden (TMB) and tumor immune dysfunction and exclusion (TIDE) of different risk groups were compared. Results: Two LUAD subtypes were determined according to the activity changes of the hallmark and immunologic gene sets. Cluster 2 had worse prognosis, more advanced tumor and clinical stages than cluster 1. Moreover, a prognostic RS signature was established using two LUAD subtype-related DEGs, which could stratify patients at different risk levels. Nomogram model incorporated RS and clinical stage exerted good prognostic performance in LUAD patients. A shorter survival time and higher TMB were observed in the high-risk patients. Conclusions: Our findings revealed that our constructed prognostic signature could exactly predict the survival status of LUAD cases, which was helpful in predicting the prognosis and guiding personalized therapeutic strategies for LUAD.

Availability, health-care costs, and utilization patterns of biologics in Taiwan.

OBJECTIVE: To provide an overview of the use of biologics in Taiwan, including the access to new biologics, the impact of this access on the growth of health-care expenditure, and the utilization patterns. METHODS: We first conducted a market-level analysis to investigate the availability of global biologics in Taiwan as well as the growth and concentration of aggregate spending on biologics. We then conducted a patient-level analysis to investigate the costs and utilization patterns for selected new biologics. RESULTS: We found that the concentration index is such that the 20 leading biologics in Taiwan account for more than 90% of the total spending on biologics. In our patient-level study on four biologics, the annual cost of treatment per patient ranged from NT$100,000 to NT$400,000. The prevalence rate of the user was between 6.5 and 37.2 per 100,000 of population. The treatment costs were inversely related to the prevalence rate of users. We also found that physicians in larger and public hospitals were more likely to prescribe new biologics to their patients compared with their counterparts practicing in smaller and private hospitals. In addition, we found that physicians were more likely to prescribe biologics to patients with more severe diseases and higher comorbidities. CONCLUSIONS: We conclude that public spending on biologics in Taiwan is highly targeted toward about 20 products with higher annual expenditures and growth rates and that the utilization of these biologics is targeted at a small number of patients. In addition, the access to these costly biologics is not uniform among patients in a country with universal coverage for prescription drugs.

New drugs and the growth of health expenditure: evidence from diabetic patients in Taiwan.

This paper contributes to the growing body of literature that debates whether the adoption of pharmaceutical innovation increases the overall expenditure on health care. By examining data obtained from Taiwan and focusing on diabetic patients, we use a new class of drugs, namely, thiazolidinediones, as an example to investigate the effect on health expenditure of prescribing new drugs to patients by focusing on the impact of treatment substitution and treatment expansion. Overall, our results indicate that the introduction of new drugs mainly impacts the outpatient drug expenditure and does not give rise to any offsetting effect on other outpatient and inpatient health expenditures. This suggests that the adoption of pharmaceutical innovation in treating diabetic patients is expenditure-increasing. In addition, we find evidence that the treatment substitution channel has a more significant impact on the level of health expenditure than the treatment expansion channel. An important policy implication for our finding is that the justification for increasing health expenditure on the treatment of diabetes is not conditional upon a lowering in the demand for other types of health-care services. By contrast, it is conditional upon the increased health benefits per se.

[Distribution and Environmental Significance of Rare Earth Elements in Typical Protected Vegetable Soil, Northern China].

The concentrations of rare earth elements (REEs) in protected vegetable soils in Wuqing district of Tianjin City, Jinzhong district of Shanxi Province, Shenyang district of Liaoning Province, and Wulanchabu district of Inner Mongolia Autonomous Region in northern China were measured to analyze the change characteristics of soil REEs in the process of protected vegetable cultivation. Additionally, we sought to use the REEs parameters to trace the feasibility of characterizing the interference of human activities on the soil ecological environment. The results showed that the total content of REEs (REE) in the topsoil of protected vegetable fields ranged from 146.52 to 158.76 mg·kg-1, with an average of 152.34 mg·kg-1 in Shenyang; 92.16 to 137.69 mg·kg-1, with an average of 115.03 mg·kg-1in Wuqing; 91.38 to 118.84 mg·kg-1, with an average of 108.03 mg·kg-1 in Wulanchabu; and 97.62 to 111.27 mg·kg-1, with an average of 102.43 mg·kg-1in Jinzhong. The REEs distribution patterns in the soils of the four areas, standardized with chondrite, characterized by a right tilt, showed that light rare earth elements were obviously enriched in the soil, demonstrated by the ratios of LREE/HREE and (La/Yb) N, which were greater than 6 and 7, respectively. The values of (La/Sm)N in the soils were higher than 3, suggesting that there was an obvious fractionation between light rare earth elements, whereas the values of (Gd/Yb)N were between 1-2, and there was a weak fractionation between heavy rare earth elements. The values of δEu in the soils were between 0.56 and 0.61, showing that Eu had a negative abnormality. The values of δCe were between 0.89 and 1.11, showing that Ce had no abnormality or weak positive abnormality. The higher LREE/HREE and (La/Yb)N in protected vegetable soil than that in open-air vegetable soil indicated the increasing differentiation degree between light and heavy rare earth elements in protected vegetable soil. The lower (La/Sm)N in protected vegetable soils indicated the reduction in the differentiation among light rare earth elements in soil. Higher δCe values and lower δEu values suggested that Ce and Eu were relatively enriched and depleted, respectively, during vegetable planting. The REE, LREE, (La/Sm)N, and δEu in protective soil decreased with the number of cultivation years, whereas the (Gd/Yb)N and δCe increased, but the HREE values did not change significantly. There was a significant correlation between δCe, δEu, (La/Yb)N, (Gd/Yb)N, and soil bulk density, soil moisture content, and soil organic matter in Tianjin protected vegetable soils, showing preliminarily that rare earth elements can be used as tracer elements to characterize the interference intensity of human activities on soil.

Two new triterpenoids from Lysimachia heterogenea Klatt and evaluation of their cytotoxicity.

Two new 13,28-epoxy oleanane-type triterpenoids, namely heterogenoside E and F, were isolated from Lysimachia heterogenea Klatt, together with the eight known compounds: palmitic acid, ß-stigmasterol, kaempferol, quercetin, hyperin, isorhamnetin, isorhamnetin-3-O-galactopyranoside and anagallisin C. Heterogenoside F possesses acetoxyl groups at the unusual C-21 and C-22 positions of its oleanane skeleton. The cytotoxic activities of anagallisin C, heterogenoside E and F were weak.

Understanding profit margins of medical providers from prescription drugs: evidence from Taiwan.

BACKGROUND: This study empirically estimates the magnitude and associated determinants of profit margins that medical providers earn from prescription drugs based on Taiwan's pharmaceutical market. METHODS: Our main data set is from the population-based claims data compiled by the National Health Insurance Research Database covering three waves of price adjustment: July-December 2004, October 2007-September 2008 and October 2009-September 2010. Only drugs whose reimbursement prices were adjusted using the R-zone formula were used as samples for this study. By calculating the difference between retail and wholesale prices for 796 pharmaceutical products, we can estimate the profit margin determinants using the regression model. RESULTS: We found evidence that suppliers of generic drugs tend to offer larger discounts to medical providers than suppliers of brand-name drugs. In addition, the countervailing power of wholesale pharmaceuticals, as measured by the discount rate offered by pharmaceutical manufacturers, is positively associated with the degree of competition within the pharmaceutical market and the size of the market itself. CONCLUSIONS: Our findings imply that the profit-seeking behaviour exhibited by medical providers is the engine of competitive forces in Taiwan's prescription drug market. This creates financial incentives for them, which in turn influences their choices of prescription drugs.

Population Aging, Technological Innovation, and the Growth of Health Expenditure: Evidence From Patients With Type 2 Diabetes in Taiwan.

OBJECTIVES: As populations are growing older, the prevalence of chronic diseases such as diabetes mellitus is rapidly increasing. Meanwhile, many new drugs are introduced each year as a result of technological advances. This study uses diabetes as an example to investigate the relative importance of population aging and technological innovation in accounting for the growth of health expenditures. METHODS: The retrospective cohort study was conducted based on claims data covering 1997 to 2006 taken from Taiwan's National Health Insurance. Patients were selected based on whether they received antidiabetic drugs. Growth in health expenditure was decomposed into 3 parts: number of patients, mean treatment cost, and the interaction between the change in the mean treatment cost and the change in the number of patients. RESULTS: The results indicated that 75% of the growth in expenditures for treating diabetic patients is attributable to the effect of population aging, as reflected by the increase in the diabetes prevalence rate (45%) and disease severity (30%). Technological innovation, in the form of treatment substitution (10%) and treatment expansion effects (15%), accounted for only about 25% of the growth in expenditures for treating diabetic patients. CONCLUSIONS: Population aging plays a more significant role than technological innovation in driving up health expenditures for the treatment of diabetic patients. This suggests that population aging may contribute significantly to the future growth of the healthcare sector in Asian countries such as Taiwan.

Synthesis, optical, and mesomorphic properties of self-assembled organogels featuring phenylethynyl framework with elaborated long-chain pyridine-2,6-dicarboxamides.

A series of new organogelators with pi-conjugated phenylethynyl framework featuring long-chain carboxamides have been synthesized. These organgelators have shown great ability to gel a variety of organic solvents to form stable organogels with the minimum gelation concentration as low as 0.1 wt %. Gelation is completely thermoreversible, and it occurs due to the aggregation of the organogelators resulting in the formation of a fibrous network via a combination of intermolecular hydrogen bonding, pi-pi stacking, and van der Waals interactions that is observed for the xerogels by TEM. The influence of sol-to-gel transition has been explored in detail by variable-temperature 1H NMR, UV-vis absorption, and fluorescence spectroscopy. Aggregation-induced enhanced emission has been observed in these organogelator molecules with an order of higher fluorescence quantum yields from solution to gels. In addition, some molecules also exhibit unique liquid crystalline properties over a large temperature range as revealed by DSC and POM studies.

Financial incentives and physicians' prescription decisions on the choice between brand-name and generic drugs: evidence from Taiwan.

This paper tests the hypothesis of whether or not financial incentives affect a physician's prescription decision on the choice of generic versus brand-name drugs within a system in which physicians prescribe and dispense drugs. By using data obtained from Taiwan and focusing on diabetic patients, our empirical results provide several consistent findings in support of the hypothesis that profit incentives do affect the physician's prescribing decision, suggesting that physicians act as imperfect agents. An important implication of our findings is that rent seeking for profit margin between the reimbursement and the acquisition price instead of reducing costs is the major driving force behind generic substitution. As a result, the providers instead of the payers or consumers reap the financial benefits of generic substitution.

Recent trends in the use of antidiabetic medications from 2008 to 2013: A nation-wide population-based study from Taiwan.

BACKGROUND: Studies from other countries indicate that utilization patterns of antidiabetic drugs change significantly after the introduction of newer classes of antidiabetic drugs (e.g. dipeptidyl peptidase-4 inhibitors [DPP-4i]). Evidence on recent trends regarding antidiabetic drug use in Taiwan is lacking, especially for times after the introduction of newer classes of drugs (e.g. DPP-4i). Therefore, the aim of the present study was to assess: (i) recent trends in the use and spending on antidiabetic drugs; (ii) changes in utilization patterns after introduction of newer classes of antidiabetic drugs; and (iii) factors associated with the choice of newer versus older classes of antidiabetic drugs. METHODS: Cases of type 2 diabetes were derived from Taiwan's National Health Insurance Research Database. Antidiabetic drug use was measured in terms of total quantity of drug exposure and healthcare spending in each calendar year from 2008 to 2103. Multiple logistic regression analysis was used to assess factors associated with drug choice. RESULTS: The use of and healthcare spending on DPP-4i increased significantly from 2008 to 2013, whereas healthcare spending on sulfonylureas decreased. For monotherapy, sulfonylureas were the most common alternatives to metformin, whereas in dual and triple antidiabetic therapies, a DPP-4i was the most common alternative to initial regimens. The use of a DPP-4i was positively associated with the use of beta-blockers, angiotensin II-converting enzyme inhibitors and/or angiotensin receptor blockers, and lipid-lowering agents, but negatively correlated with age, hypertension, severity of diabetes complications, and the use of diuretics and calcium channel blockers. CONCLUSIONS: With growing spending on newer antidiabetic drugs, future research on the comparative cost-effectiveness and safety of antidiabetic drugs is anticipated.

Comparative cost-effectiveness of metformin-based dual therapies associated with risk of cardiovascular diseases among Chinese patients with type 2 diabetes: Evidence from a population-based national cohort in Taiwan.

OBJECTIVE: To assess the cost-effectiveness of metformin-based dual therapies associated with cardiovascular disease (CVD) risk in a Chinese population with type 2 diabetes. METHODS: We utilized Taiwan's National Health Insurance Research Database (NHIRD) 1997-2011, which is derived from the claims of National Health Insurance, a mandatory-enrollment single-payer system that covers over 99% of Taiwan's population. Four metformin-based dual therapy cohorts were used, namely a reference group of metformin plus sulfonylureas (Metformin-SU) and metformin plus acarbose, metformin plus thiazolidinediones (Metformin-TZD), and metformin plus glinides (Metformin-glinides). Using propensity scores, each subject in a comparison cohort was 1:1 matched to a referent. The effectiveness outcome was CVD risk. Only direct medical costs were included. The Markov chain model was applied to project lifetime outcomes, discounted at 3% per annum. The bootstrapping technique was performed to assess uncertainty in analysis. RESULTS: Metformin-glinides was most cost-effective in the base-case analysis; Metformin-glinides saved $194 USD for one percentage point of reduction in CVD risk, as compared to Metformin-SU. However, for the elderly or those with severe diabetic complications, Metformin-TZD, especially pioglitazone, was more suitable; as compared to Metformin-SU, Metformin-TZD saved $840.1 USD per percentage point of reduction in CVD risk. Among TZDs, Metformin-pioglitazone saved $1831.5 USD per percentage point of associated CVD risk reduction, as compared to Metformin-rosiglitazone. CONCLUSIONS: When CVD is considered an important clinical outcome, Metformin-pioglitazone is cost-effective, in particular for the elderly and those with severe diabetic complications.

Multistimuli-Responsive Luminescence of Naphthalazine Based on Aggregation-Induced Emission.

Stimuli-responsive luminescent materials, which are dependent on changes in physical molecular packing modes, have attracted more and more interest over the past ten years. In this study, 2,2-dihydroxy-1,1-naphthalazine was synthesized and shown to exhibit different fluorescence emission in solution and solid states with characteristic aggregation-induced emission (AIE) properties. A remarkable change in the fluorescence of 2,2-dihydroxy-1,1-naphthalazine occurred upon mechanical grinding, heating, or exposure to solvents. According to the characterization by solid-state fluorescence spectroscopy, X-ray crystallography, differential scanning calorimetry, and X-ray powder diffraction, the fluorescence change could be attributed to transitions between two structurally different polymorphs. These significant properties could also give 2,2-dihydroxy-1,1-naphthalazine more potential applications as a multifunctional material.