Search

Atherosclerosis caused major morbidity and mortality worldwide. Molecules possessing lipid-lowering and/or anti-inflammatory properties are potential druggable targets against atherosclerosis. We examined the anti-atherosclerotic effects of fluorescent gold nanoclusters (FANC), which were dihydrolipoic acid (DHLA)-capped 2-nm gold nanoparticles. We evaluated the 8-week effects of FANC in Western-type diet-fed ApoE-deficient mice by either continuous intraperitoneal delivery (20 μM, 50 μl weekly) or via drinking water (300 nM). FANC reduced aortic atheroma burden, serum total cholesterol, and oxidative stress markers malondialdehyde and 4-hydroxynonenal levels. FANC attenuated hepatic lipid deposit, with changed expression of lipid homeostasis-related genes HMGCR, SREBP, PCSK9, and LDLR in a pattern similar to mice treated with ezetimibe. FANC also inhibited intestinal cholesterol absorption, resembling the action of ezetimibe. The lipid-lowering and anti-atherosclerotic effects of FANC reappeared in Western-type diet-fed LDLr-deficient mice. FANC bound insulin receptor β (IRβ) via DHLA, leading to AKT activation. However, unlike insulin, which also bound IRβ to activate AKT to induce HO-1, activation of AKT by FANC was independent of HO-1 expression in human aortic endothelial cells (HAECs). Alternatively, FANC up-regulated NRF2, interfered the binding of KEAP1 to NRF2, and promoted KEAP1 degradation to free NRF2 for nuclear entry to induce HO-1 that suppressed the expression of ICAM-1 and VCAM-1. Consistently, FANC suppressed ox-LDL-induced enhanced attachment of THP-derived macrophages onto HAECs. In macrophages, FANC up-regulated ABCA1, and reversed ox-LDL-induced suppression of cholesterol efflux. FANC effected in vitro at nano moles. In conclusion, our findings showed novel actions and multiple mechanisms of FANC worked coherently against atherosclerosis.

Background: Tricuspid regurgitation (TR) is the most common tricuspid valve (TV) condition. However, little is known about the prevalence, clinical significance, or economic impact of TR, including TR with comorbid heart failure (HF). Materials and Methods: Taiwan’s National Health Insurance Research Database was used to perform a retrospective cohort study about patients with TR. The study included patients over the age of 18 with TR who provided data from January 2017 to December 2019. The cohorts were divided into six groups based on whether significant TR was present (sTR) or not (nsTR), and whether HF was present (HF) or not present (noHF), or inconclusive (incHF). Results: This study included 21,051 patients with TR. Patients with nsTR-noHF had an annualized healthcare burden of 0.36 all-cause hospitalizations, 3.26 days length of stay (LOS), and NTD 66,834 in expenses. sTR led to significant increases in healthcare utilization and expenditures. The annualized economic burden for sTR-noHF patients increased to 1.03 all-cause hospitalizations, 10.75 days LOS, and NTD 210,842 in expenses. Patients with sTR and HF had significantly higher healthcare utilization and expenditures; patients with sTR-HF had an annualized economic burden of 2.46 all-cause hospitalizations, 33.18 days LOS, and NTD 480,711 in spending. Conclusion: TR patients with HF or sTR are more likely to be hospitalized, use more healthcare resources, and face higher financial burdens.

BackgroundThe Taiwanese government adopted the National Health Insurance (NHI) system in March 1995. This study aimed to understand the difference in medication costs before (year 2019) and during the COVID-19 pandemic (2020–2021) among different hospitals for treating their patients.MethodsThe NHI claims database consisting of claims of prescription drugs for inpatients (IPD) and outpatients (OPD) in Taiwan was used to determine drug expenditure in different hospitals, particularly the top 10 prescription Anatomical Therapeutic Chemical (ATC) categories.ResultsIn medical centers, L01X (other antineoplastic agents) showed the highest drug expenditure, followed by L04A (immunosuppressants) and J05A (direct-acting antivirals). The drug expenditure pattern in regional hospitals was similar to that in medical centers, with L01X (other antineoplastic agents) showing the highest drug expenditure. L01X (other antineoplastic agents) also showed the highest drug expenditure in district hospitals, followed by N05A (antipsychotics) and A10B (blood glucose-lowering drugs, excluding insulin). In clinics, A10B (blood glucose-lowering drugs, excluding insulin) showed the highest drug expenditure. The total medication costs in 2021 were lower or similar to those in 2019. The use of systemic use anti-infectives decreased over time in OPDs among all hospita1 levels but increased in IPDs in medical centers and district hospitals. Furthermore, our analysis revealed that the trend in drug expenditure closely mirrored the trend in drug prescription volume for the highest annual sum cost item among the top 10 drug subgroups across different hospital levels.ConclusionOur analysis found that annual drug expenditures in 2021 were lower or similar to those in 2019, suggesting that the COVID-19 pandemic has contributed to this reduction in drug expenditure.

Background: Hepatocellular carcinoma (HCC) is a major contributor to the world’s cancer burden. Understanding the HCC incidence rate in Taiwan is thus an interesting avenue of research. Methods: From an NHI database, those patients who had been newly diagnosed with HCC and who had been listed on a registry in a catastrophic illness dataset during the years 2013–2021 were enrolled in this study. Antineoplastic agent usage and comorbidities were also studied. Results: The incidence rate of HCC decreased from 57.77 to 44.95 in 100,000 from 2013 to 2021. The average age of patients with HCC increased from 65.54 years old with a CCI score of 4.98 in 2013 to 67.92 years old with a CCI score of 5.49 in 2021. Among these HCC patients, the patients under antineoplastic agent treatment decreased from 53.47% to 31.41% from 2013 to 2021. The presence of comorbidities in HCC patients was about 55.77–83.01% with mild liver disease and 29.93–37.30% with diabetes (without complications) in the period 2013–2021. Conclusions: The incidence rate of HCC slightly decreased in Taiwan. Due to antineoplastic agent usage decreasing over time, these results may indicate that more early-stage HCC patients detected in recent years were mainly treated with surgeries.

Abstract Background Marginally low birth weight (MLBW) is defined as a birth weight of 2000 ~ 2499 g. Inconsistent findings have been reported on whether children with low birth weight had higher rates of neurological, attention, or cognitive symptoms. No studies have explored the occurrence of clinically diagnosed psychiatric disorders in term- born MLBW infants. We aimed to investigate the risk of subsequent psychiatric disorders in term-born children with MLBW. Methods This is a nationwide retrospective cohort study, by analysing the data from Taiwan’s National Health Insurance Research Database from 2008 to 2018. The study population includes propensity-score-matched term-born infants with MLBW and those without MLBW (birth weight ≥ 2500 g). Cox proportional hazard analysis was used after adjustment for potential demographic and perinatal comorbidity confounders. Incidence rates and hazard ratios (HR) of 11 psychiatric clinical diagnoses were evaluated. Results A total of 53,276 term-born MLBW infants and 1,323,930 term-born infants without MLBW were included in the study. After propensity score matching for demographic variables and perinatal comorbidities, we determined that the term-born MLBW infants (n = 50,060) were more likely to have attention deficit and hyperactivity disorder (HR = 1.26, 95% confidence interval (CI) [1.20, 1.33]), autism spectrum disorder (HR = 1.26, 95% CI [1.14, 1.40]), conduct disorder (HR = 1.25, 95% CI [1.03, 1.51]), emotional disturbance (HR: = 1.13, 95% CI [1.02, 1.26]), or specific developmental delays (HR = 1.38, 95% CI [1.33, 1.43]) than term-born infants without MLBW (n = 50,060). Conclusion MLBW was significantly associated with the risk of subsequent psychiatric disorder development among term-born infants. The study findings demonstrate that further attention to mental health and neurodevelopment issues may be necessary in term-born children with MLBW. However, possibilities of misclassification in exposures or outcomes, and risks of residual and unmeasured confounding should be concerned when interpreting our data.

Abstract Introduction Mitral regurgitation (MR) is characterized by systolic blood flow reversal from the left ventricle to the left atrium. A 2019 study indicated that in the USA, clinically significant MR (sMR) is associated with a substantial healthcare cost burden. In Taiwan, few data are available to describe the clinical characteristics, treatment patterns, and economic burden of patients with sMR. Methods Using the National Health Insurance Research Database (NHIRD), a national, detailed claims database of all 23 million residents of Taiwan, we conducted a retrospective cohort study to identify patients with sMR and quantify the impact of the disease on Taiwan’s healthcare system. We classified patients with sMR into three cohorts based on disease etiology: functional MR (sFMR), degenerative MR (sDMR), and uncharacterized MR (sUMR). Results We compared patient characteristics across cohorts and estimated attributable healthcare utilization and costs during the 12-month follow-up period. Our research shows that in Taiwan, patients with sFMR were older, sicker, and presented at casualty (emergency department) more frequently than those with sDMR and sUMR. Meanwhile, patients with sDMR had the highest 12-month healthcare expenditures across the cohorts. Conclusion These findings are inconsistent with what has been shown in the USA, which warrants further investigation.

Abstract Cardiovascular disease (CVD) is strongly associated with the gut microbiota and its metabolites, including trimethylamine-N-oxide (TMAO), formed from metaorganismal metabolism of ʟ-carnitine. Raw garlic juice, with allicin as its primary compound, exhibits considerable effects on the gut microbiota. This study validated the benefits of raw garlic juice against CVD risk via modulation of the gut microbiota and its metabolites. Allicin supplementation significantly decreased serum TMAO in ʟ-carnitine-fed C57BL/6 J mice, reduced aortic lesions, and altered the fecal microbiota in carnitine-induced, atherosclerosis-prone, apolipoprotein E-deficient (ApoE−/−) mice. In human subjects exhibiting high-TMAO production, raw garlic juice intake for a week reduced TMAO formation, improved gut microbial diversity, and increased the relative abundances of beneficial bacteria. In in vitro and ex vivo studies, raw garlic juice and allicin inhibited γ-butyrobetaine (γBB) and trimethylamine production by the gut microbiota. Thus, raw garlic juice and allicin can potentially prevent cardiovascular disease by decreasing TMAO production via gut microbiota modulation.

ObjectiveAortic stenosis (AS) is a heart valve disease characterized by left ventricular outflow fixed obstruction. It can be managed by surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). However, real-world evidence for TAVI or SAVR outcomes is lacking in Taiwan. This study aimed to compare the clinical outcomes of TAVI and SAVR for treating of AS in Taiwan.Materials and methodsThe National Health Insurance Research Database is a nationally representative cohort that contains detailed registry and claims data from all 23 million residents of Taiwan. This retrospective cohort study used this database to compare patients who underwent SAVR (bioprosthetic valves) or TAVI from 2017 to 2019. Survival outcomes and length of hospital stay (LOS) and intensive care unit (ICU) stay between TAVI and SAVR in the matched cohort. A Cox proportional hazards model was performed to identify the effect of treatment type on survival rates while controlling variables including age, gender, and comorbidities.ResultsWe identified 475 and 1605 patients who underwent TAVI and SAVR with a bioprosthetic valve, respectively. Patients who underwent TAVI were older (82.19 vs. 68.75 y/o) and more likely to be female (55.79% vs. 42.31%) compared with patients who underwent SAVR. Propensity score matching (PSM) on age, gender, and Elixhauser Comorbidity Index (ECI) score revealed that 375 patients who underwent TAVI were matched with patients who underwent SAVR. A significant difference was found in survival rates between TAVI and SAVR. The 1-year mortality rate was 11.44% with TAVI and 17.55% with SAVR. Both the mean total LOS (19.86 vs. 28.24 days) and mean ICU stay (6.47 vs. 11.12 days) for patients who underwent TAVI were shorter than those who underwent SAVR.ConclusionPatients who had undergone TAVI had better survival outcomes and shorter LOS compared with patients who had undergone SAVR in Taiwan.

Aim: This study aimed to understand themedication usage among different hospitals in Taiwan. Materials & methods: The NHI claims database consisting of claims prescription drugs in Taiwan was used to determine drug prescriptions in different hospitals. Results: In the medical center, L01X showed the highest drug expenditure and the drug prescription pattern in regional hospitals was similar to that in the medical center. The highest drug expenditure in the district hospital and clinics was A10B. Conclusion: Our analysis suggests that the annual pharmaceutical expenditures from 2016 to 2018 were increasing over time in all hospitals. The generic drug usage in medical centers/regional hospitals was lower than district hospitals/clinics.

Abstract The capability of gut microbiota in degrading foods and drugs administered orally can result in diversified efficacies and toxicity interpersonally and cause significant impact on human health. Production of atherogenic trimethylamine N-oxide (TMAO) from carnitine is a gut microbiota-directed pathway and varies widely among individuals. Here, we demonstrated a personalized TMAO formation and carnitine bioavailability from carnitine supplements by differentiating individual TMAO productivities with a recently developed oral carnitine challenge test (OCCT). By exploring gut microbiome in subjects characterized by TMAO producer phenotypes, we identified 39 operational taxonomy units that were highly correlated to TMAO productivity, including Emergencia timonensis, which has been recently discovered to convert γ-butyrobetaine to TMA in vitro. A microbiome-based random forest classifier was therefore constructed to predict the TMAO producer phenotype (AUROC = 0.81) which was then validated with an external cohort (AUROC = 0.80). A novel bacterium called Ihubacter massiliensis was also discovered to be a key microbe for TMA/TMAO production by using an OCCT-based humanized gnotobiotic mice model. Simply combining the presence of E. timonensis and I. massiliensis could account for 43% of high TMAO producers with 97% specificity. Collectively, this human gut microbiota phenotype-directed approach offers potential for developing precision medicine and provides insights into translational research. Video Abstract

Abstract Background Streptococcus pneumoniae (S. pneumoniae) and non-typeable Haemophilus influenzae (NTHi) are substantial contributors to morbidity and mortality of diseases including invasive pneumococcal diseases (IPDs), pneumonia and acute otitis media (AOM) worldwide. In Taiwan, 10-valent pneumococcal polysaccharide and NTHi protein D conjugate vaccine (PHiD-CV) and 13-valent pneumococcal conjugate vaccine (PCV13) are licensed in children against pneumococcal disease. In addition to S. pneumoniae, clinical trials suggest efficacy of PHiD-CV against NTHi AOM. This study aims at evaluating the cost-effectiveness of a 2 + 1 schedule of PHiD-CV vs. PCV13 2 + 1 in the universal mass vaccination program of infants in Taiwan. Methods A published Markov cohort model was adapted to simulate the epidemiological burden of IPD, pneumonia and AOM for a birth cohort in Taiwan over 10 years. The probability of entering a specific health state was based on the incidence rate of the diseases. Only direct medical costs were included, and costs and outcomes were discounted annually. Vaccine efficacy assumptions were based on published data and validated by a panel of independent experts. Clinical, epidemiological, and serotype distribution data were based on locally published data or the National Health Insurance Research Database. Price parity of vaccines was assumed. Published pneumococcal disease-related disutility weights were used due to lack of local data. Incremental cost-effectiveness ratio was calculated and benchmarked against the recommended threshold in Taiwan. Extensive one-way sensitivity analysis, alternative scenarios and probabilistic sensitivity analysis were performed to test the robustness of the results. Results PHiD-CV would potentially reduce the number of NTHi-related AOM cases substantially and prevent comparable IPD and pneumonia-related cases and deaths compared to PCV13. Over a 10-year horizon, PHiD-CV is estimated to dominate PCV13, saving 6.7 million New Taiwan Dollars (NTD) and saving 21 quality-adjusted life years. The result was robust over a wide range of sensitivity analyses. The dominance of PHiD-CV was demonstrated in 90.5% of the simulations. Conclusions PHiD-CV 2 + 1 would provide comparable prevention of IPD, pneumonia cases and additional reduction of NTHi-AOM cases, and is considered dominant compared with PCV13 2 + 1 in Taiwan.

Respiratory syncytial virus (RSV) is a major burden of disease in babies and young children, including hospitalizations and deaths. RSV is a seasonal disease that peaks when temperatures decrease in temperate zones and humidity increases in tropical regions. Existing research reveals that RSV hospitalization activity is year-round in Taiwan, which is a subtropical region with small peaks in spring and fall. The monthly distribution and COVID-19 pandemic impact were unclear. The aim of this study was to investigate Taiwan’s RSV hospitalization seasonality and the COVID-19 pandemic effects. The National Health Insurance Database and Death Registration Files from the Center for Health and Welfare Data Science Center were connected to birth data for this study. RSV hospitalization (RSVH) in infants aged 0–1 years ranged from 0.9518% (2009) to 1.7113% (2020), substantially higher than in children aged 1–5. Most years had 2 or 3 RSV epidemic seasons in 0–5-year-olds over the 13-year follow-up. RSVH incidence was low until the autumn of 2020, when a major rise occurred after September and lasted until December 2020. We detected RSVH peaks in February–May and July–August. The 2020 RSV outbreak was found at the end of 2020.

Fluorescent gold nanoclusters conjugated with α-lipoic acid (FANC) is a promising biocompatible fluorescent nanomaterial with a high potential for drug development. However, there is still no FANC-related research on toxicology, which is very important for future research and the development of healthy food supplements or drugs. This study uses oral administration of FANC to determine the most appropriate dose range in ICR mice for further evaluation. The in vivo acute and subacute toxicity study was conducted by oral administration of FANC to male and female ICR mice. Animal survival, body weight, daily food consumption, hematological profile, organ coefficient, serum biochemistry profile, and histopathological changes were analyzed. FANC did not show any form of morbidity or mortality at acute and subacute toxicity in both male and female ICR mice. Animal behavior, daily food consumption, hematological profile, organ coefficient, and histopathology showed no treatment-related malignant changes at single and repeated doses. Furthermore, serum glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), and creatinine (CRE) levels showed no significant malignant changes, which indicated that FANC does not cause liver and renal damage. The only change observed in this study was the change in body weight. The body weight of the FANC-treated group was slightly decreased in female mice but increased in male mice; however, the body weight decreases were below the threshold of concern, and there was no dose–response effect. In conclusion, no observed adverse effect level (NOAEL) in repeated doses was considered in 20 μM/100 μL/25 g male and female ICR mice.

Abstract Background Antrodia cinnamomea is an indigenous medicinal mushroom in Taiwan, commonly used for the treatment of cancers and inflammatory disorders. 4-acetylantroquinonol B (4AAQB) is one of the active component isolated from the mycelium of A. cinnamomea. However, whether 4AAQB exhibits anti-inflammatory effect is not clear. Methods The anti-inflammatory activity of 4AAQB was examined by ELISA to measure the pro-inflammatory cytokines production in lipopolysaccharide (LPS)-simulated RAW264.7 cells, peritoneal macrophages and in mice. The effect of 4AAQB for MAPK kinase molecules phosphorylation in LPS-stimulated RAW264.7 macrophage including ERK, JNK and p38 were evaluated. The in vivo efficacy of 4AAQB was also demonstrated. Results In the present study, we found that 4AAQB exhibits anti-inflammatory effects inhibit tumor necrosis factor-α (TNF-α)/interleukin-6 (IL-6) releasing and LPS-stimulated phagocytes migration without affect cell growth. In addition, the MAPK kinase molecules phosphorylation in LPS-stimulated RAW264.7 macrophage including ERK, JNK and p38 was inhibited by 4AAQB. The phosphorylation of NFκB subunit p65 and IkBα were also decreased after 4AAQB treatment. Furthermore, 4AAQB attenuates the cytokine production in LPS-induced and CLP-induced septic mice. Conclusion These results showed that 4AAQB exhibited anti-inflammatory property both in vitro and in vivo, suggesting that 4AAQB may be a therapeutic candidate which used in inflammatory disorders treatment.

An amendment to this paper has been published and can be accessed via the original article.

Polymer polyethylene glycol (PEG), or PEGylation of polypeptides improves protein drug stability by decreasing degradation and reducing renal clearance. To produce a pharmaceutical disintegrin derivative, the N-terminal PEGylation technique was used to modify the disintegrin derivative [KGDRR]trimucrin for favorable safety, pharmacokinetic profiles, and antithrombotic efficacy. We compared intact [KGDRR]trimucrin (RR) and PEGylated KGDRR (PEG-RR) by in vitro and in vivo systems for their antithrombotic activities. The activity of platelet aggregation inhibition and the bleeding tendency side effect were also investigated. PEG-RR exhibited optimal potency in inhibiting platelet aggregation of human/mouse platelet-rich plasma activated by collagen or ADP with a lower IC50 than the intact derivative RR. In the illumination-induced mesenteric venous thrombosis model, RR and PEG-RR efficaciously prevented occlusive thrombosis in a dose-dependent manner. In rotational thromboelastometry assay, PEG-RR did not induce hypocoagulation in human whole blood even given at a higher concentration (30 μg/mL), while RR slightly prolonged clotting time. However, RR and PEG-RR were not associated with severe thrombocytopenia or bleeding in FcγRIIa-transgenic mice at equally efficacious antithrombotic dosages. We also found the in vivo half-life of PEGylation was longer than RR (RR: 15.65 h vs. PEG-RR: 20.45 h). In conclusion, injectable PEG-RR with prolonged half-life and decreased bleeding risk is a safer anti-thrombotic agent for long-acting treatment of thrombus diseases.

OBJECTIVES:To assess the nationwide seasonal peaks, risk factors, and utilization of medical resources of respiratory syncytial virus-associated hospitalization (RSVH) in preterm infants in Taiwan. STUDY DESIGN:A Taiwan nationwide birth cohort was extracted from the Birth Certificate Application Database during 2007-2009 and prospectively linked to the National Health Insurance database. We evaluated the seasonal peaks and risk factors (gestational age [GA], chronologic age [CA], and bronchopulmonary dysplasia [BPD]) associated with the RSVH of preterm infants. The length of hospital stays (LOS), care in intensive care unit (ICU), and use of mechanical ventilation (MV) were also analyzed. RESULTS:There is a total duration of 9 months of RSVH season in Taiwan, three seasonal peaks and two seasonal peaks of RSVH in preterm infants with BPD and without BPD, respectively. Preterm infants had significantly higher RSVH rate than term infants (2.6% vs 0.9%, p

Abstract Background Melanoma is an aggressive skin cancer and a predominant cause of skin cancer-related deaths. A previous study has demonstrated the ability of butein to inhibit tumor proliferation and invasion. However, the anti-metastatic mechanisms and in vivo effects of butein have not been fully elucidated. Methods MTT cell viability assays were used to evaluate the antitumor effects of butein in vitro. Cytotoxic effects of butein were measured by lactate dehydrogenase assay. Anti-migratory effects of butein were evaluated by two-dimensional scratch and transwell migration assays. Signaling transduction and VEGF-releasing assays were measured by Western blotting and ELISA. We also conducted an experimental analysis of the metastatic potential of tumor cells injected into the tail vein of C57BL/6 mice. Results We first demonstrated the effect of butein on cell viability at non-cytotoxic concentrations (1, 3, and 10 μM). In vitro, butein was found to inhibit the migration of B16F10 cells in a concentration-dependent manner using transwell and scratch assays. Butein had a dose-dependent effect on focal adhesion kinase, Akt, and ERK phosphorylation in B16F10 cells. Butein efficiently inhibited the mTOR/p70S6K translational inhibition machinery and decreased the production of VEGF in B16F10 cells. Furthermore, the in vivo antitumor effects of butein were demonstrated using a pulmonary metastasis model. Conclusion The results of the present study indicate the potential utility of butein in the treatment of melanoma.

Snake venoms affect blood coagulation and platelet function in diverse ways. Some venom components inhibit platelet function, while other components induce platelet aggregation. Among the platelet aggregation inhibitors, disintegrins have been recognized as unique and potentially valuable tools for examining cell−matrix and cell−cell interactions and for the development of antithrombotic and antiangiogenic agents according to their anti-adhesive and anti-migration effect on tumor cells and antiangiogenesis activities. Disintegrins represent a family of low molecular weight, cysteine-rich, Arg-Gly-Asp(RGD)/Lys-Gly-Asp(KGD)-containing polypeptides, which inhibit fibrinogen binding to integrin αIIbβ3 (i.e., platelet glycoprotein IIb/IIIa), as well as ligand binding to integrins αvβ3, and α5β1 expressed on cells (i.e., fibroblasts, tumor cells, and endothelial cells). This review focuses on the current efforts attained from studies using disintegrins as a tool in the field of arterial thrombosis, angiogenesis, inflammation, and tumor metastasis, and briefly describes their potential therapeutic applications and side effects in integrin-related diseases. Additionally, novel R(K)GD-containing disintegrin TMV-7 mutants are being designed as safer antithrombotics without causing thrombocytopenia and bleeding.

The prevalence of diabetes has increased worldwide. To obtain nationwide data on accountability and utilization of health resources among diabetes patients in Taiwan, an analysis of the claims data for the National Health Insurance (NHI) from 2000 to 2009 was conducted. Methods: One-third of the NHI claims database was randomly sampled from 2000 to 2009. Diabetes was defined by three or more outpatient visits with diagnostic codes [International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM): 250 or A code: A181] within 1 year, or one inpatient discharge diagnosis. Accountability items and NHI codes of various metabolic parameters and examinations were identified. Medical utilization was measured by the frequency and cost of care associated with ambulatory visits, hospitalizations, and emergency care within each year. Results: The annual check-up frequency for various examinations significantly increased from 2000 to 2009. Both the average outpatient department (OPD) cost per diabetes patient/year and the average inpatient department (IPD) cost per time increased 1.34-fold in the past decade. The average OPD cost per diabetes patient and average IPD cost of each admission for diabetes patients was four times and 1.4 times compare with the general population, respectively. The annual average medical cost of each diabetes patient affected with both micro- and macrovascular complications was four times compared with those without vascular complications. There was an increasing trend for diabetes patients to visit regional hospital for OPD and IPD, whereas visits to the local hospital decreased in the past decade. Conclusion: Due to the increased frequency of annual check-ups after various examinations, the quality of diabetes management has improved in the past decade in Taiwan. As diabetes patients affected with both micro- and macrovascular complications incurred costs four times compared with those without complications, it is worth screening high-risk individuals to ensure earlier intervention and thus reduce diabetic complications and healthcare expenditure.

The impact of the introduction of newer anti-diabetic agents on the treatment pattern in the booming diabetic population remains unclear. We examined the patterns and temporal trends of anti-diabetic drug use in Taiwan, with particular emphasis on combination therapy. Methods: We searched the Taiwan National Health Insurance Database during 2000–2009 to identify outpatient prescriptions of anti-diabetic drugs, including human insulins and insulin analogues, sulfonylureas, glinides, metformin, thiazolidinediones, alpha-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors. Glucose-lowering treatments were classified according to pattern (oral agents only, insulins only, and oral agents and insulins combined) and a number of different classes of anti-diabetic drugs. Insulin therapy and combination therapy with two oral anti-diabetic drugs (OAD) were further classified according to individual drug combination patterns. Results: Although metformin remained the mainstay of anti-diabetic treatment, patients receiving combination therapy of oral glucose-lowering agents, either with or without insulin, significantly increased, from approximately 40% in 2000 to 60% in 2009, particularly in relation to the newer agents, including glinides, alpha-glucosidase inhibitors, and long-acting insulin analogues. Use of sulfonylureas and thiazolidinediones decreased substantially. For insulin therapy, the most commonly prescribed drugs were premix insulin analogues and basal insulin analogues, accounting for one-third of total insulin prescriptions in 2009. Conclusion: We found an increasing complexity of anti-diabetic therapy during the past decade in Taiwan. Further studies are needed to evaluate whether this treatment pattern will lead to improved clinical outcomes in terms of cost-effectiveness.

Cardiovascular complication is the leading cause of mortality in patients with diabetes. Dyslipidemia and hypertension are the major risk factors contributing to cardiovascular disease (CVD). This study was carried out to investigate the prevalence of dyslipidemia and hypertension and their associations with microvascular and macrovascular complications in patients with type 2 diabetes in Taiwan. Methods: Health-care data and diagnostic codes were retrieved from the Taiwan Bureau of National Health Insurance claims files for the years 2000–2009. Based on these data the annual prevalences of dyslipidemia and hypertension were calculated and patients were stratified by age, gender, and diabetic complications. Results: In patients with diabetes, the prevalence of dyslipidemia increased with age, with the highest rate recorded in adults (inclusive of both genders) between 40 and 65 years of age (p for trend 65 years of age (p for trend

Diabetes is one of the leading causes of dialysis, blindness, and amputation worldwide. However, the prevalence of diabetes-related kidney, eye, and foot diseases has not been investigated in national surveys. Methods: In this study, we reviewed data sets of the National Health Insurance claims for the years 2000–2009. In 2009, the total population of Taiwan was 23 million. We de-identified the data and then analyzed them on inpatients and outpatients with diabetes mellitus, kidney diseases, eye diseases, peripheral vascular diseases (PVDs), and diabetic foot according to the International Classification of Diseases, 9th Revision with Clinical Modification diagnosis codes. Results: The prevalence of diabetic nephropathy increased from 13.32% in 2000 to 15.42% in 2009. The corresponding diabetes dialysis rate increased from 1.5% to 2.46% during the same period (p

Medical systems and care for diabetes have changed greatly in Taiwan in recent years. This study investigated mortality trends in patients with diabetes in Taiwan from 2000 to 2009. Methods: We linked the National Health Insurance (NHI) claims database, which contains data on 99% of the population of Taiwan, to the National Death Registry and Cancer Registry. Patients were classified as having diabetes if they had at least one hospital admission or three or more outpatient visits with a diabetes diagnostic code in each calendar year. Mortality data from the Collaboration Center of Health Information Application were used to estimate age- and sex-specific mortality rates, all-cause mortality, and life expectancy (LE). Results: The mortality of patients with diabetes in Taiwan decreased continuously from 2000 to 2009 for both sexes and all age groups; the mortality rate was generally higher for men than for women (3.92% vs. 3.29% in 2000; 3.64% vs. 3.11% in 2005, and 3.12% vs. 2.71% in 2009, all p