[Effect of acupuncture combined with low frequency rTMS on comorbid mild-to-moderate depressive disorder and insomnia: a randomized controlled trial].

OBJECTIVE: To observe the impacts of acupuncture on depressive mood and sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia, and explore its effect mechanism. METHODS: A total of 60 patients with comorbid mild-to-moderate depressive disorder and insomnia were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 2 cases dropped off). In the observation group, acupuncture and low frequency repeated transcranial magnetic stimulation (rTMS) were combined for the intervention. Acupuncture was applied to Baihui (GV 20), Yintang (GV 24+), Neiguan (PC 6) and Yanglingquan (GB 34), etc., the needles were retained for 30 min; and the intradermal needles were embedded at Xinshu (BL 15) and Danshu (BL 19) for 2 days. After acupuncture, the rTMS was delivered at the right dorsolateral prefrontal cortex (R-DLPFC), with 1 Hz and 80% of movement threshold, lasting 30 min in each treatment. In the control group, the sham-acupuncture was adopted, combined with low frequency rTMS. The acupoint selection and manipulation were the same as the observation group. In the two groups, acupuncture was given once every two days, 3 times weekly; while, rTMS was operated once daily, for consecutive 5 days a week. The duration of treatment consisted of 4 weeks. Hamilton depression scale-17 (HAMD-17) and Pittsburgh sleep quality index (PSQI) scores were observed before and after treatment, as well as 1 month after the treatment completion (follow-up period) separately. Besides, the levels of nerve growth factor (BDNF) and γ-aminobutyric acid (GABA) in the serum were detected before and after treatment in the two groups. RESULTS: After treatment and in follow-up, the HAMD-17 scores were lower than those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than the control group (P<0.05). After treatment, the total scores and the scores of each factor of PSQI were reduced in the two groups in comparison with those before treatment except for the score of sleep efficiency in the control group (P<0.05); the total PSQI score and the scores for sleep quality, sleep latency, sleep efficiency and daytime dysfunction in the observation group were all lower than those in the control group (P<0.05). In the follow-up, except for the scores of sleep duration and sleep efficiency in the control group, the total PSQI score and the scores of all the other factors were reduced compared with those before treatment in the two groups (P<0.05); the total PSQI score and the scores of sleep quality, sleep latency, sleep duration, sleep efficiency and daytime dysfunction in the observation group were lower than the control group (P<0.05). After treatment, the levels of serum BDNF and GABA were increased in comparison with those before treatment in the observation group (P<0.05), and the level of serum BDNF was higher than that in the control group (P<0.05). CONCLUSION: Acupuncture relieves depressive mood and improves sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia. The effect mechanism may be related to the regulation of BDNF and GABA levels and the promotion of brain neurological function recovery.

[Effect of electroacupuncture at back-shu points of five zang on fatigue status and cortical excitability in chronic fatigue syndrome].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at back-shu points of five zang on fatigue status, quality of life and motor cortical excitability in patients with chronic fatigue syndrome (CFS), so as to explore the possible mechanism of EA for CFS. METHODS: A total of 72 patients with CFS were randomized into an EA group (36 cases, 4 cases dropped off) and a sham EA group (36 cases, 3 cases dropped off). In the EA group, EA at Ganshu (BL 18), Xinshu (BL 15), Pishu (BL 20), Feishu (BL 13) and Shenshu (BL 23) was adopted, with continuous wave, 2 Hz in frequency. In the sham EA group, sham EA at non-acupoints (1.5-2.0 cm lateral to back-shu points of five zang) was applied, with shallow needling, and no current was connected. The treatment in the both groups was 20 min each time, once every other day, 2 weeks as one course, 3 courses were required. Before and after treatment, the scores of fatigue scale-14 (FS-14) and the MOS 36-item short form health survey (SF-36) were observed, and cortical excitability (the resting motor threshold [RMT], amplitude of motor-evoked potential [MEP-A] and latency of motor-evoked potential [MEP-L]) was detected in the two groups. RESULTS: After treatment, the physical fatigue score, mental fatigue score and total score of FS-14, as well as RMT of motor cortex in the EA group were decreased compared with those before treatment (P<0.01), the physical fatigue score and total score of FS-14 in the sham EA group were decreased compared with those before treatment (P<0.05); each item score and total score of FS-14 and RMT of motor cortex in the EA group were lower than those in the sham EA group (P<0.01, P<0.05). After treatment, each item score and total score of SF-36 and MEP-A of motor cortex in the EA group were increased compared with those before treatment (P<0.01), which were higher than those in the sham EA group (P<0.01, P<0.05). CONCLUSION: EA at back-shu points of five zang can effectively improve the fatigue status and quality of life in patients with CFS, its mechanism may be related to the up-regulating excitability of cerebral motor cortex.

[FU Wen-bin's experience in treatment of depression complicated with obsessive-compulsive disorder from perspective of heart and gallbladder].

Based on the thinking of integrative and holistic acupuncture and moxibustion, FU Wen -bin proposes to treat depression complicated with obsessive-compulsive disorder from perspective of heart and gallbladder. In clinical practice, the treatment pattern of "acupuncture at the top priority, followed by moxibustion, and consolidation at the end" is applied, acupuncture, refined moxibustion, intradermal needle and other therapies are comprehensively adopted, acupoints on the heart meridian, pericardium meridian and gallbladder meridian are selected or back-shu points and front-mu points of the heart, gallbladder and pericardium are matched, and the acupoints on the conception vessel and governor vessel and with the functions of tonifying kidney and regulating qi are added to calm the heart and tranquilize the mind, so as the symptoms of depression and obsessive-compulsive can be effectively relieved.

Chinese medicine for residual symptoms of COVID-19 recovered patients (long COVID)-A double-blind, randomized, and placebo-controlled clinical trial protocol.

Introduction: Coronavirus disease 2019 (COVID-19) is the current global pandemic of which residual symptoms exhibited by post-acute, rehabilitating patients include fatigue, dyspnoea, and insomnia. Chinese medicine (CM) has been widely used in China to treat different stages of COVID-19. While there are a significant number of clinical studies suggesting its efficacy and safety in its use during acute stage, there are very few randomized controlled trials focusing on the rehabilitation stage. Liujunzhi Decoction and Shashen Maidong Decoction are frequently recommended by official clinical guidelines in China to treat COVID-19 patients in rehabilitation stage. This double-blind, randomized, placebo controlled study aims to evaluate the efficacy and safety of the combination of the two formulae [named "COVID-19 Rehab Formula (CRF)"] in treating COVID-19 residual symptoms (long COVID). Methods: Eligible subjects will be randomly divided into treatment group and control group in 1:1 ratio. Treatment group will receive CRF along with certain pre-defined CM according to symptoms for 8 weeks, while control group will receive equivalent packs of placebo for 8 weeks. Data in terms of Fatigue Severity Score (FSS), self-reported COVID-19 long term symptom assessment, the modified British Medical Research Council (mMRC) Dyspnoea Scale, EuroQol Five-Dimension Five-Level (EQ-5D-5L) Questionnaire, pulmonary function test and adverse events will be collected and analyzed by SPSS 24. Blood test on liver and renal functions will also be conducted as safety measures. Conclusion: This study will evaluate the efficacy and safety of CRF in the treatment COVID-19 residual symptoms in a scientifically rigorous design. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT04924881].

MiR-195 inhibits the ubiquitination and degradation of YY1 by Smurf2, and induces EMT and cell permeability of retinal pigment epithelial cells.

The dysregulated microRNAs (miRNAs) are involved in diabetic retinopathy progression. Epithelial mesenchymal transition (EMT) and cell permeability are important events in diabetic retinopathy. However, the function and mechanism of miR-195 in EMT and cell permeability in diabetic retinopathy remain largely unclear. Diabetic retinopathy models were established using streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-stimulated ARPE-19 cells. Retina injury was investigated by hematoxylin-eosin (HE) staining. EMT and cell permeability were analyzed by western blotting, immunofluorescence, wound healing, and FITC-dextran assays. MiR-195 expression was detected via qRT-PCR. YY1, VEGFA, Snail1, and Smurf2 levels were detected via western blotting. The interaction relationship was analyzed via ChIP, Co-IP, or dual-luciferase reporter assay. The retina injury, EMT, and cell permeability were induced in STZ-induced diabetic mice. HG induced EMT and cell permeability in ARPE-19 cells. MiR-195, YY1, VEGFA, and Snail1 levels were enhanced, but Smurf2 abundance was reduced in STZ-induced diabetic mice and HG-stimulated ARPE-19 cells. VEGFA knockdown decreased Snail1 expression and attenuated HG-induced EMT and cell permeability. YY1 silence reduced VEGFA and Snail1 expression, and mitigated HG-induced EMT and cell permeability. YY1 could bind with VEGFA and Snail1, and it was degraded via Smurf2-mediated ubiquitination. MiR-195 knockdown upregulated Smurf2 to decrease YY1 expression and inhibited HG-induced EMT and cell permeability. MiR-195 targeted Smurf2, increased expression of YY1, VEGFA, and Snail1, and promoted HG-induced EMT and cell permeability. MiR-195 promotes EMT and cell permeability of HG-stimulated ARPE-19 cells by increasing VEGFA/Snail1 via inhibiting the Smurf2-mediated ubiquitination of YY1.

A randomized controlled trial to assess the effectiveness and safety of acupuncture for overactive bladder: a study in Hong Kong population.

BACKGROUND: Around 15% of the Hong Kong population was found to suffer from overactive bladder (OAB), but the current available treatments, such as medication, behavioral therapy and physical therapy are unsatisfactory. Previous studies have suggested that acupuncture may have promising effect for OAB, but some limitations on the study design render the evidence questionable. This study aimed to evaluate the effectiveness and safety of acupuncture treatment for patients with OAB in Hong Kong. METHODS: One hundred patients with OAB were enrolled. The patients were randomized to receive either active acupuncture or sham needle intervention twice a week for 8 consecutive weeks, and had a follow-up consultation 12 weeks after the completion of acupuncture intervention. The primary outcome assessment was the 3-Day Voiding Diary, which records daytime and night-time urinary frequency and symptoms, at the baseline, the end of the 8-week intervention and 12 weeks after acupuncture intervention. Secondary outcomes included Urine NGF level, Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6), as well as Overactive Bladder Symptom Score (OABSS). RESULTS: After 16 sessions of treatment, when compared with the baseline, both active and sham acupuncture significantly reduced the frequency of urgency urinary incontinence (UUI), daytime and night-time urinary frequency as well as the scores of IIQ-7, UDI-6 and OABSS. Moreover, the treatment effects could last for at least 3 months. However, no significant difference in frequency of UUI and daytime urinary frequency was found between the active and sham acupuncture groups. On the other hand, the night-time urinary frequency decreased more significantly during the treatment and follow-up in the active acupuncture group than in the sham control group after controlling baseline night-time urinary frequency. Urine NGF level could not be detected by ELISA method in our experiments. CONCLUSION: This study suggests a beneficial effect of acupuncture on improving OAB symptoms. Both active and sham acupuncture treatment were able to improve the symptoms of frequency of urgency urinary incontinence, and the daytime and night-time urinary frequency, while only mild adverse effects were found. This project was unable to establish the specific effect of acupuncture for OAB.Trial registration Chinese Clinical Trial Registry, ChiCTR-INR-16010048. Registered on 29 Nov 2016.

Candidemia due to uncommon Candida species in children: new threat and impacts on outcomes.

Many uncommon Candida spp. (species other than C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, and C. krusei) have been shown to emerge in tertiary care facilities. We aimed to investigate these uncommon candidemia in children. Forty-six cases of candidemia caused by uncommon Candida spp. were identified during 2003-2015 from a medical center in Taiwan. The most common specie was C. guilliermondii (31.2%), followed by C. lusitaniae (18.8%) and C. metapsilosis (18.8%). These cases were analyzed and compared with 148 episodes of C. albicans candidemia. The incidence density of uncommon Candida spp. candidemia and the proportion to all candidemia episodes increased substantively during the study period. Prior exposure to azoles was uncommon in the 30 days prior to infection, but fluconazole resistant strains were significantly more common (n = 19, 41.3%). The increased incidence density of uncommon Candida spp. candidemia was associated with increasing use of antifungal agents. No differences in demographics, underlying comorbidities, risk factors, clinical features, dissemination, and 30-day mortality were found between uncommon Candida spp. and C. albicans candidemia. Patients with uncommon Candida spp. candidemia were more likely to require modifications in antifungal treatment and receive echinocandin drugs (43.5% vs 21.6%, p = 0.007). Candidemia caused by uncommon Candida spp. had poorer response to antifungal treatment, led to longer duration of candidemia (median 4.0 versus 2.5 days, p = 0.008), and had a higher treatment failure rate (56.5% vs 38.5%, p = 0.040).

Discovery of chiral dihydropyridopyrimidinones as potent, selective and orally bioavailable inhibitors of AKT.

During the course of our research efforts to develop potent and selective AKT inhibitors, we discovered enatiomerically pure substituted dihydropyridopyrimidinones (DHP) as potent inhibitors of protein kinase B/AKT with excellent selectivity against ROCK2. A key challenge in this program was the poor physicochemical properties of the initial lead compound 5. Integration of structure-based drug design and physical properties-based design resulted in replacement of a highly hydrophobic poly fluorinated aryl ring by a simple trifluoromethyl that led to identification of compound 6 with much improved physicochemical properties. Subsequent SAR studies led to the synthesis of new pyran analog 7 with improved cell potency. Further optimization of pharmacokintetics properties by increasing permeability with appropriate fluorinated alkyl led to compound 8 as a potent, selective AKT inhibitors that blocks the phosphorylation of GSK3ß in vivo and had robust, dose and concentration dependent efficacy in the U87MG tumor xenograft model.

Comparing effects between music intervention and aromatherapy on anxiety of patients undergoing mechanical ventilation in the intensive care unit: a randomized controlled trial.

PURPOSE: Using patient-reported outcomes and physiological indicators to test the effects of music intervention and aromatherapy on reducing anxiety for intensive care unit (ICU) patients undergoing mechanical ventilation. METHODS: Patients with ICU admission duration >24 h were randomly assigned to a Music intervention group (n = 41), Aromatherapy group (n = 47), or Control group (rest only; n = 44). Each patient in the Music group listened to music; each patient in the Aromatherapy group received lavender essential oil massage on his/her back for 5 min; each patient in the Control group wore noise-canceling headphones. Anxiety was measured using the Chinese version of the Stage-Trait Anxiety Inventory (C-STAI) and the Visual Analogue Scale for Anxiety (VAS-A) at baseline, post-test, and 30-min follow-up. Heart rate, breathing rate, and blood pressure were measured every 10 min from baseline to the 30-min follow-up. RESULTS: The Music group had significantly better post-test VAS-A and C-STAI scores, and had lower heart rate and blood pressure than the Control group. The Aromatherapy group had significantly better VAS-A score and lower heart rate than the Control group. The 30-min follow-up showed that both Music and Aromatherapy groups had lower heart rate and blood pressure than the Control group. CONCLUSIONS: Music and aromatherapy interventions were both effective for ICU patients. The effects of music intervention were greater than that of aromatherapy; both interventions maintained the effects for at least 30 min.

Dipeptidyl Peptidase-4 Inhibitor Use Is Not Associated With Acute Pancreatitis in High-Risk Type 2 Diabetic Patients: A Nationwide Cohort Study.

To analyze the association between use of DPP-4 inhibitors and acute pancreatitis in high-risk type 2 diabetic patients. A retrospective nationwide cohort study was conducted using the Taiwan National Health Insurance claim database. The risk associated with sitagliptin was compared to that with acarbose, a second-line antidiabetic drug prescribed for patients with similar diabetes severity and with a known neutral effect on pancreatitis. Between January 1, 2009 and December 31, 2010, a total of 8526 sitagliptin initiators and 8055 acarbose initiators who had hypertriglyceridemia or prior hospitalization history for acute pancreatitis were analyzed for the risk of hospitalization due to acute pancreatitis stratified for baseline propensity score. In the crude analysis, sitagliptin was associated with a decreased risk of acute pancreatitis (hazard ratio [HR] 0.74; 95% confidence interval [CI]: 0.62-0.88) compared to acarbose in diabetic patients with prior history of hospitalization for pancreatitis or hypertriglyceridemia. The association was abolished after stratification for propensity score quintiles (adjusted HR 0.95; 95% CI: 0.79-1.16). Similar results were found separately in both patients' histories of prior hospitalization of acute pancreatitis (adjusted HR 0.97; 95% CI: 0.76-1.24) and those with hypertriglyceridemia (adjusted HR 0.86; 95% CI: 0.65-1.13). No significant association was found for different durations or accumulative doses of sitagliptin. In the stratified analysis, no significant effect modification was found in relation to patients' characteristics. Use of sitagliptin was not associated with an increased risk of acute pancreatitis in high-risk diabetic patients with hypertriglyceridemia or with history of acute pancreatitis.

Comparative Cardiovascular and Cerebrovascular Safety of Inhaled Long-Acting Bronchodilators in Patients with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study.

STUDY OBJECTIVE: Inhaled long-acting bronchodilators are commonly used as maintenance therapy in chronic obstructive pulmonary disease (COPD). We compared the risk of cardiovascular and cerebrovascular events among patients with COPD treated with inhaled long-acting bronchodilator monotherapy and combination therapy. DESIGN: Retrospective cohort study. SETTINGS: A population-based health care database from Taiwan. PATIENTS: Individuals with COPD who initiated long-acting muscarinic antagonists (LAMAs) alone, long-acting ß-2 agonists (LABA) alone, and LABA and LAMA in combination between 2001 and 2010. MEASUREMENTS AND MAIN RESULTS: We used Cox regression models to compare a composite cardiovascular outcome, defined as hospitalization for acute myocardial infarction, congestive heart failure, and cerebrovascular diseases among the three treatment groups, adjusting for potential confounders. Among a cohort of 3458 study-eligible patients, we identified 505 composite cardiovascular events during 10,590 patient-years of follow-up. In the primary analysis which considered first exposure carried forward, LABA alone and LAMA alone were associated with similar risks of the composite outcome (hazard ratio [HR] 1.09; 95% confidence interval [CI] 0.87-1.37). The HR comparing LABA and LAMA in combination with LAMA alone was 1.13 (95% CI 0.60-2.13) and to LABA alone was 1.03 (95% CI 0.55-1.92). The secondary analysis in which we allowed patients to reenter the cohort upon treatment change yielded similar results, but with slightly higher HRs comparing LABA and LAMA in combination with LAMA alone (HR 1.26, 95% CI 0.74-2.15) and to LABA alone (HR 1.31, 95% CI 0.80-2.13). CONCLUSIONS: Our results suggest similar cardiovascular and cerebrovascular safety of LABA and LAMA when agents are used alone. Additional studies are needed to rule out potential risk associated with inhaled long-acting bronchodilator combination therapy.

Therapeutic inertia and intensified treatment in diabetes mellitus prescription patterns: A nationwide population-based study in Taiwan.

Objective To measure therapeutic inertia by characterizing prescription patterns using secondary data obtained from the nationwide diabetes mellitus pay-for-performance (DM-P4P) programme in Taiwan. Methods Using reimbursement claims from Taiwan's National Health Insurance Research Database, a nationwide retrospective cohort study was undertaken of patients with diabetes mellitus who participated in the DM-P4P programme from 2006-2008. Glycosylated haemoglobin results were used to evaluate modifications in therapy in response to poor diabetes control. Prescription patterns were used to assign patients to either a therapeutic inertia group or an intensified treatment group. Therapeutic inertia was defined as the failure to act on a known problem. Results The research sample comprised of 168 876 patients with diabetes mellitus who had undergone 899 135 tests. Of these, 37.4% (336 615 visits) of prescriptions were for a combination of two types of drug and 27.7% (248 788 visits) were for a combination of three types of drug. The proportion of patients in the intensified therapy group who were prescribed more than two types of drug was considerably higher than that in the therapeutic inertia group. Conclusion In many cases in the therapeutic inertia group only a single type of hypoglycaemic drug was prescribed or the dosage remained unchanged.

Participating physician preferences regarding a pay-for-performance incentive design: a discrete choice experiment.

OBJECTIVE: To determine whether the magnitude of incentives or other design attributes should be prioritized and the most important attributes, according to physicians, of the diabetes P4P (pay-for-performance) program design. DESIGN: We implemented a discrete choice experiment (DCE) to elicit the P4P incentive design-related preferences of physicians. PARTICIPANTS: All of the physicians (n = 248) who participated in the diabetes P4P program located in the supervisory area of the northern regional branch of the Bureau of National Health Insurance in 2009 were included. The response rate was ∼ 60%. RESULTS: Our research found that the bonus type of incentive was the most important attribute, followed by the incentive structure and the investment magnitude. CONCLUSIONS: Physicians may feel that good P4P designs are more important than the magnitude of the investment by the insurer. The two most important P4P designs include providing the bonus type of incentive and using pay-for-excellence plus pay-for-improvement.

Antimitotic and antivascular activity of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes.

This study reports the synthesis of a series of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes, which are potent antitubulin agents. Compound 13, (2-hydroxy-3,4,5-trimethoxyphenyl)-(6-methoxy-1H-indol-3-yl)-methanone exhibits marked antiproliferative activity against KB and MKN45 cells with IC50 values of 8.8 and 10.5 nM, respectively, binds strongly to the colchicine binding site and leads to inhibition of tubulin polymerization. It also behaves as a vascular disrupting agent which suppresses the formation of capillaries. The C2-OH group in the A-ring of this compound not only retains the biological activity but has valuable physicochemical properties.

Effects of rhodiola crenulata on mice hearts under severe sleep apnea.

BACKGROUND: The goal of this study is to determine if Rhodiola Crenulata (RC) has protective effects on mice hearts with severe sleep apnea model. METHODS: Sixty-four C57BL/6 J mice 5-6 months old were distributed into 4 groups i.e. Control group (21% O2, 24 h per day, 8 weeks, n=16); Hypoxia group (Hypoxia: 7% O2 60 s, 20% O2 alternating 60 s, 8 h per day, 8 weeks, n=16); Hypoxia+90RC and Hypoxia+270RC group (Hypoxia for 1st 4 weeks and hypoxia pretreated 90 mg/Kg and 270 mg/Kg Rhodiola Crenulata by oral gavage per day for 2nd 4 weeks, each n=16). Excised hearts from 4 groups of mice were analyzed for heart weight index changes using H&E staining, TUNEL-positive assays and Western Blotting protein. RESULTS: Cardiac widely dispersed TUNEL-positive apoptotic cells in mice hearts were less in Hypoxia+RC90 and Hypoxia+RC270 than those in Hypoxia. Compared with Hypoxia, the protein levels of Fas ligand, Fas death receptors, Fas-Associated Death Domain (FADD), activated caspase 8, and activated caspase 3 (Fas dependent apoptotic pathways) were decreased in Hypoxia+RC90, Hypoxia+RC270. The protein levels of Bad, Bax, t-Bid, activated caspase 9, activated caspase 3 (mitochondria dependent apoptotic pathway) were less in Hypoxia+RC90, Hypoxia+RC270 than those in hypoxia. The protein levels of Bcl2, Bcl-xL, p-Bad (Bcl2-realted anti-apoptotic pathway) and VEGF, p-PI3k, p-AKT (VEGF-related pro-survival pathway) were higher in Hypoxia+RC90, Hypoxia+RC270 than those in hypoxia. CONCLUSIONS: Our findings suggest that Rhodiola Crenulata have protective effects on chronic intermittent hypoxia-induced cardiac widely dispersed apoptosis via Fas-dependent and mitochondria-dependent apoptotic and VEGF-related pro-survival pathway.

Cardiovascular risk associated with acarbose versus metformin as the first-line treatment in patients with type 2 diabetes: a nationwide cohort study.

CONTEXT: Metformin is the first-line oral therapy for type 2 diabetes with proven benefits against cardiovascular risk. Recent evidence suggested that acarbose might be similar to metformin in glucose-lowering efficacy and cardiovascular risk reduction. Therefore, international guidelines have suggested the use of acarbose as alternative first-line antidiabetic therapy. OBJECTIVE: To compare the cardiovascular outcomes in the first-line users of acarbose vs metformin. DESIGN, SETTING, PATIENTS, AND OUTCOME MEASURES: A nationwide cohort study was conducted by analyzing the Taiwan National Health Insurance (NHI) Database. A total of 17,366 acarbose initiators and 230,023 metformin initiators were identified between January 1, 2009 and December 31, 2010. The primary outcome is hospitalization due to any cardiovascular events, including acute myocardial infarction, congestive heart failure, and ischemic stroke. The propensity score method was used to adjust for baseline differences between the two groups. Patients were followed from drug initiation to the earliest of outcome occurrence, death or disenrollment from NHI, or study termination. RESULTS: In intention-to-treat analyses, acarbose was associated with a higher risk of any cardiovascular event (adjusted hazard ratio [HR]: 1.05; 95% confidence interval [CI], 1.01-1.09), heart failure (HR, 1.08; 95% CI, 1.00-1.16), and ischemic stroke (HR, 1.05, 95% CI, 1.00-1.10) than metformin. No significant difference in risk was found in subgroups of patients with or without underlying hypertension, ischemic heart disease, or cerebrovascular disease. Similar results were found in auxiliary as-treated analyses or analyses stratified by propensity score quintiles. CONCLUSION: Our data do not support that acarbose has a cardio-protective effect similar to metformin as a first-line antidiabetic agent.

Significant reduction in end-stage liver diseases burden through the national viral hepatitis therapy program in Taiwan.

UNLABELLED: A national viral hepatitis therapy program was launched in Taiwan in October 2003. This study aimed to assess the impact of the program on reduction of end-stage liver disease (ESLD) burden. Profiles of national registries of households, cancers, and death certificates were used to derive incidence and mortality of ESLDs from 2000 to 2011. Age-gender-adjusted incidence and mortality rates of hepatocellular carcinoma (HCC) and chronic liver diseases (CLDs) and cirrhosis of adults ages 30-69 years were compared before and after launching the program using Poisson's regression models. A total of 157,570 and 61,823 patients (15%-25% of those eligible for reimbursed treatment) received therapy for chronic hepatitis B and C, respectively, by 2011. There were 42,526 CLDs and cirrhosis deaths, 47,392 HCC deaths, and 74,832 incident HCC cases occurred in 140,814,448 person-years from 2000 to 2011. Male gender and elder age were associated with a significantly increased risk of CLDs and cirrhosis and HCC. Mortality and incidence rates of ESLDs decreased continuously from 2000 to 2003 (before therapy program) through 2004-2007 to 2008-2011 in all age and gender groups. The age-gender-adjusted rate ratio (95% confidence interval; P value) in 2008-2011 was 0.78 (0.76-0.80; P < 0.001) for CLDs and cirrhosis mortality, 0.76 (0.75-0.78; P < 0.005) for HCC mortality, and 0.86 (0.85-0.88; P < 0.005) for HCC incidence using 2000-2003 as the reference period (rate ratio = 1.0). CONCLUSIONS: The national viral hepatitis therapy program has significantly reduced the mortality of CLDs and cirrhosis and incidence and mortality of HCC.

Effectiveness and safety of extracranial carotid stent placement: a nationwide self-controlled case-series study.

BACKGROUND: Carotid angioplasty and stent (CAS) placement has emerged as an attractive revascularization strategy for patients with internal carotid artery stenosis. However, the effectiveness and safety of CAS were not fully evaluated, mainly because of methodological difficulties in finding an appropriate comparison group. METHODS: Patients who underwent CAS were identified from Taiwan's National Health Insurance claims database between 2005 and 2008. The incidence rate of ischemic stroke after CAS was compared with that of the year prior to the procedure using a self-controlled case series analysis and a conditional Poisson regression model. Logistic regression was conducted to identify factors associated with poor outcome. RESULTS: A total of 1258 patients who had undergone CAS were included, and 73 cases (5.8%) of death or ischemic stroke occurred during the index hospitalization. Within 1 year after CAS, 74 patients died and 80 experienced an ischemic stroke. Of the 1184 patients who were followed for 360 days, the rate ratio for ischemic stroke decreased to 0.21 (95% CI: 0.08-0.51) between 31 and 180 days, and 0.10 (95% CI: 0.03-0.32) between 181 and 360 days. Statin therapy was associated with a reduced risk of death or ischemic stroke in the 1(st) month (odds ratio of 0.53; 95% CI: 0.32-0.90). Conversely, the use of nonsteroidal anti-inflammatory agents, possibly histamine-2 receptor blockers, and CAS performed by low-volume operators were associated with a twofold increased risk. CONCLUSION: CAS reduced the long-term risk for ischemic stroke. Self-controlled case series analysis might be an appropriate design for evaluating device safety and effectiveness.

Concordance between patient self-reports and claims data on clinical diagnoses, medication use, and health system utilization in Taiwan.

PURPOSE: The aim of this study was to evaluate the concordance between claims records in the National Health Insurance Research Database and patient self-reports on clinical diagnoses, medication use, and health system utilization. METHODS: In this study, we used the data of 15,574 participants collected from the 2005 Taiwan National Health Interview Survey. We assessed positive agreement, negative agreement, and Cohen's kappa statistics to examine the concordance between claims records and patient self-reports. RESULTS: Kappa values were 0.43, 0.64, and 0.61 for clinical diagnoses, medication use, and health system utilization, respectively. Using a strict algorithm to identify the clinical diagnoses recorded in claims records could improve the negative agreement; however, the effect on positive agreement and kappa was diverse across various conditions. CONCLUSION: We found that the overall concordance between claims records in the National Health Insurance Research Database and patient self-reports in the Taiwan National Health Interview Survey was moderate for clinical diagnosis and substantial for both medication use and health system utilization.

Impacts of drug reimbursement reductions on utilization and expenditures of oral antidiabetic medications in Taiwan: an interrupted time series study.

OBJECTIVES: To control increasing pharmaceutical expenditures, Taiwan's National Health Insurance has implemented a series of drug reimbursement price reductions since 2000. This study examined changes in use and expenditures of oral antidiabetic medications following the price regulation in November 2006. METHODS: We obtained claims data between January 2006 and August 2007 from Taiwan's National Health Insurance Research Database. We categorized oral antidiabetic products as affected by the reimbursement reduction ("targeted") or not ("non-targeted"), by level of relative price reduction, and by manufacturer type (international vs. local manufacturers). We used an interrupted time series design and segmented regression models to estimate changes in monthly per capita prescribing rate, volume, and insurance reimbursement expenditures following the policy. RESULTS: The majority (129/178; 72.5%) of oral antidiabetic products were targeted by this round of price reductions. There was a relative reduction of 9.5% [95%CI: -12.68, -6.32] in total expenditures at ten months post-policy compared to expected rates. For targeted products, there were 2.04% [95%CI: -4.15, 0.07] and 13.26% [95%CI: -16.64, -9.87] relative reductions in prescribing rate and expenditures, respectively, at ten months post-policy. Non-targeted products increased significantly (22% [95%CI: 10.49, 33.51] and 22.85% [95%CI: 11.69, 34.01] relative increases in prescribing rate and expenditures respectively). Larger reimbursement cuts led to greater reductions in prescribing rate, volume, and insurance reimbursement expenditures of targeted products. Prescribing rates of both targeted and non-targeted products by international manufacturers declined after the policy while rates of prescribing non-targeted products by local manufacturers increased. CONCLUSIONS: While total government expenditures for oral antidiabetic medications were contained by the policy, our results indicate that prescribing shifted at the margin from targeted to non-targeted products and from international to local products. Further research is warranted to understand how changes in medication use due to price regulation policies affect medication adherence and patient health outcomes.