Kuo-Liong Chien

Effect of antidiabetic agents added to metformin on glycaemic control, hypoglycaemia and weight change in patients with type 2 diabetes: a network meta-analysis.

Aim: Most guidelines recommend metformin as first‐line therapy in patients with type 2 diabetes. However, the choice of a second‐line drug lacks consistent consensus. We aimed to assess available information of antidiabetic drugs added to metformin on the change in glycated haemoglobin A1c (A1C), risk of hypoglycaemia and change in body weight.

Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-analysis

Objective To assess the effects of different classes of antihypertensive treatments, including monotherapy and combination therapy, on survival and major renal outcomes in patients with diabetes. Design Systematic review and bayesian network meta-analysis of randomised clinical trials. Data sources Electronic literature search of PubMed, Medline, Scopus, and the Cochrane Library for studies published up to December 2011. Study selection Randomised clinical trials of antihypertensive therapy (angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), α blockers, β blockers, calcium channel blockers, diuretics, and their combinations) in patients with diabetes with a follow-up of at least 12 months, reporting all cause mortality, requirement for dialysis, or doubling of serum creatinine levels. Data extraction Bayesian network meta-analysis combined direct and indirect evidence to estimate the relative effects between treatments as well as the probabilities of ranking for treatments based on their protective effects. Results 63 trials with 36 917 participants were identified, including 2400 deaths, 766 patients who required dialysis, and 1099 patients whose serum creatinine level had doubled. Compared with placebo, only ACE inhibitors significantly reduced the doubling of serum creatinine levels (odds ratio 0.58, 95% credible interval 0.32 to 0.90), and only β blockers showed a significant difference in mortality (odds ratio 7.13, 95% credible interval 1.37 to 41.39). Comparisons among all treatments showed no statistical significance in the outcome of dialysis. Although the beneficial effects of ACE inhibitors compared with ARBs did not reach statistical significance, ACE inhibitors consistently showed higher probabilities of being in the superior ranking positions among all three outcomes. Although the protective effect of an ACE inhibitor plus calcium channel blocker compared with placebo was not statistically significant, the treatment ranking identified this combination therapy to have the greatest probability (73.9%) for being the best treatment on reducing mortality, followed by ACE inhibitor plus diuretic (12.5%), ACE inhibitors (2.0%), calcium channel blockers (1.2%), and ARBs (0.4%). Conclusions Our analyses show the renoprotective effects and superiority of using ACE inhibitors in patients with diabetes, and available evidence is not able to show a better effect for ARBs compared with ACE inhibitors. Considering the cost of drugs, our findings support the use of ACE inhibitors as the first line antihypertensive agent in patients with diabetes. Calcium channel blockers might be the preferred treatment in combination with ACE inhibitors if adequate blood pressure control cannot be achieved by ACE inhibitors alone.

The relationship between serum galectin-3 and serum markers of cardiac extracellular matrix turnover in heart failure patients

BACKGROUND A growing body of evidence links macrophage activation and fibrosis to the pathogenesis of heart failure (HF). Galectin-3 is one of the most likely mediators between macrophage activation and myocardial fibrosis. However, the exact relationship is unknown in humans. We assessed the impact of galectin-3 on serum markers of cardiac extracellular matrix (ECM) turnover in HF patients. METHODS Patients with HF manifestations and a left ventricular ejection fraction (LVEF) <or=50% were enrolled in this study. Gender, age, medications, serum biochemical data, and outcomes of heart failure were recorded. Serum galectin-3, extracellular matrix including type I and III aminoterminal propeptide of procollagen (PINP and PIIINP), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were analyzed. RESULTS A total of 106 (83 males and 23 females) patients were enrolled. The age was 61+/-16 y and LVEF was 35+/-9%. Their mean NYHA functional class was 2.2. Log galectin-3 was significantly correlated with log PIIINP (p=0.006), log TIMP-1 (p=0.025), log MMP-2 (p=0.016), and NYHA functional class (p=0.034); but not age, sex or LVEF. After adjusting for age, sex, smoking status and LVEF, the relationship between galectin-3 and ECM turnover biomarkers (including PIIINP, TIMP, and MMP-2) remained significant. After adjusting for age, sex, smoking status and NYHA functional class, the relationship between galectin-3 and PIIINP or MMP-2 remained significant. CONCLUSIONS Galectin-3 is significantly correlated with serum markers of cardiac ECM turnover in HF patients. This implies a relationship between macrophage activation and ECM turnover in patients with HF.

Treatment of low back pain by acupressure and physical therapy: randomised controlled trial

Abstract Objective To evaluate the effectiveness of acupressure in terms of disability, pain scores, and functional status. Design Randomised controlled trial. Setting Orthopaedic clinic in Kaohsiung, Taiwan. Participants 129 patients with chronic low back pain. Intervention Acupressure or physical therapy for one month. Main outcome measures Self administered Chinese versions of standard outcome measures for low back pain (primary outcome: Roland and Morris disability questionnaire) at baseline, after treatment, and at six month follow-up. Results The mean total Roland and Morris disability questionnaire score after treatment was significantly lower in the acupressure group than in the physical therapy group regardless of the difference in absolute score (- 3.8, 95% confidence interval - 5.7 to - 1.9) or mean change from the baseline (- 4.64, - 6.39 to - 2.89). Acupressure conferred an 89% (95% confidence interval 61% to 97%) reduction in significant disability compared with physical therapy. The improvement in disability score in the acupressure group compared with the physical group remained at six month follow-up. Statistically significant differences also occurred between the two groups for all six domains of the core outcome, pain visual scale, and modified Oswestry disability questionnaire after treatment and at six month follow-up. Conclusions Acupressure was effective in reducing low back pain in terms of disability, pain scores, and functional status. The benefit was sustained for six months.

Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis

BACKGROUND Major adjuvant treatments for pancreatic adenocarcinoma include fluorouracil, gemcitabine, chemoradiation, and chemoradiation plus fluorouracil or gemcitabine. Since the optimum regimen remains inconclusive, we aimed to compare these treatments in terms of overall survival after tumour resection and in terms of grade 3-4 toxic effects with a systematic review and random-effects Bayesian network meta-analysis. METHODS We searched PubMed, trial registries, and related reviews and abstracts for randomised controlled trials comparing the above five treatments with each other or observation alone before April 30, 2013. We estimated relative hazard ratios (HRs) for death and relative odds ratios (ORs) for toxic effects among different therapies by combining HRs for death and survival durations and ORs for toxic effects of included trials. We assessed the effects of prognostic factors on survival benefits of adjuvant therapies with meta-regression. FINDINGS Ten eligible articles reporting nine trials were included. Compared with observation, the HRs for death were 0·62 (95% credible interval 0·42-0·88) for fluorouracil, 0·68 (0·44-1·07) for gemcitabine, 0·91 (0·55-1·46) for chemoradiation, 0·54 (0·15-1·80) for chemoradiation plus fluorouracil, and 0·44 (0·10-1·81) for chemoradiation plus gemcitabine. The proportion of patients with positive lymph nodes was inversely associated with the survival benefit of adjuvant treatments. After adjustment for this factor, fluorouracil (HR 0·65, 0·49-0·84) and gemcitabine (0·59, 0·41-0·83) improved survival compared with observation, whereas chemoradiation resulted in worse survival than fluorouracil (1·69, 1·12-2·54) or gemcitabine (1·86, 1·04-3·23). Chemoradiation plus gemcitabine was ranked the most toxic, with significantly higher haematological toxic effects than second-ranked chemoradiation plus fluorouracil (OR 13·33, 1·01-169·36). INTERPRETATION Chemotherapy with fluorouracil or gemcitabine is the optimum adjuvant treatment for pancreatic adenocarcinoma and reduces mortality after surgery by about a third. Chemoradiation plus chemotherapy is less effective in prolonging survival and is more toxic than chemotherapy. FUNDING None.

Chin-Shan Community Cardiovascular Cohort in Taiwan–baseline data and five-year follow-up morbidity and mortality

A cohort consisting of 3602 residents (82.8% of the target population) aged 35 years and older was established in 1990 in the Chin-Shan Community, a suburb 20 miles outside of metropolitan Taipei, Taiwan. The long-term objective was to investigate the prospective impact on cardiovascular health in a society undergoing transition from a developing to a developed nation. This article presents the study design, selected baseline risk factors of cardiovascular diseases (CVD), and CVD events at the 5-year follow-up evaluation with an emphasis on sociodemographic differences. The multivariate logistic regression analyses revealed that white-collar individuals were more likely than blue-collar workers to have dyslipidemia including high-density lipoprotein cholesterol (HDL-C) levels <35 mg/dl [odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.2-2.4] and low-density lipoprotein cholesterol (LDL-C) levels >/=160 mg/dl (OR = 1.3, 95% CI = 1.0-1.7). However, they were at slightly lower risk for stroke and CVD/sudden death, and at moderately higher risk for coronary artery disease and diabetes, although both these trends were not significant. Men were more likely than women to have HDL-C levels <35 mg/dl (OR = 1.8, 95% CI = 1.4-2.2), but they were less likely to have LDL-C levels >/=160 mg/dl (OR = 0.7, 95% CI = 0.6-0.8). The risk of CVD/sudden death was higher for men than for women during the follow-up period (OR = 1.9, 95% CI = 1.3-2.9). This could be due to risk factors such as a much higher prevalence of tobacco (61.9% vs. 4.5%) and alcohol (43.7% vs. 6.4%) use in men. In conclusion, individuals of higher socioeconomic status have a higher prevalence of dyslipidemia but slightly lower 5-year incidence of CVD events.

Uric acid level as a risk marker for metabolic syndrome: A Chinese cohort study

OBJECTIVE Despite some epidemiologic research demonstrating a positive relationship between serum uric acid (SUA) levels and the prevalence of metabolic syndrome (MetS), prospective data on SUA as a predictor of MetS incidence are limited. METHODS The authors examined SUA as a risk marker for incident MetS in a prospective study of 3857 subjects who were free of MetS at baseline recruitment. Hyperuricemia was defined as SUA ≥7.7 mg/dL for men and ≥6.6 mg/dL for women. The MetS was defined according to a unified criteria set by several major organizations. RESULTS During a mean follow-up of 5.41 years, 476 participants developed MetS. A significantly stepwise increase in the incidence of MetS across tertiles of SUA was observed in the whole group (p for trend <0.001). Among women, this association was more robust than in men. After adjustment for age, variations of blood pressure, triglycerides, HDL-C, glucose, and waist circumference, females in the middle and upper tertiles of SUA had significantly higher risk of developing MetS when compared with subjects in the lowest tertile [adjusted-HR (95% CI) was 1.67 (1.12-2.49) and 3.18 (2.20-4.60), respectively; p for trend <0.001]. Overall, hyperuricemia was a significantly independent risk determinant for MetS in women, but it was a non-significant factor for MetS mediating waist circumference and serum triglycerides in men. CONCLUSION SUA concentration is more closely associated with MetS in females than in males. Future investigations are needed to explore the underlying mechanisms involved in the sex-related association between SUA concentration and MetS risk.

The graded effect of hyperhomocysteinemia on the severity and extent of coronary atherosclerosis

It is not clear to what extent methylenetetrahydrofolate reductase (MTHFR) gene and hyperhomocysteinemia effect the severity and extent of coronary atherosclerosis in Asian populations. We examined the MTHFR genotypes and plasma homocysteine (HCY) concentrations in 192 Taiwanese and investigated their relationship with coronary artery disease (CAD), and the severity and extent of coronary atherosclerosis. The distribution of MTHFR genotypes was similar in 116 CAD patients and 76 non-CAD subjects. Homozygosity was noted in 8% of CAD patients and 13% of non-CAD subjects (P=0.33; 95% CI, 0. 2-1.6). The geometric mean of HCY values was higher in CAD patients (11.10+/-1.51 micromol/l) than in non-CAD subjects (9.21+/-1.55 micromol/l) (P=0.003). HCY levels were higher in patients with multi-vessel disease (P<0.05) or in patients with > or = 90% stenotic lesions (P=0.005), compared with non-CAD subjects. The CAD risks in the top two HCY quartiles (> or = 14.0 and 10.1-13.9 micromol/l) were 4.0 (95% CI, 1.7-9.2) and 3.2 (95% CI, 1.4-7.4) times higher than in the lowest quartile (< or = 7.9 micromol/l) (P=0.001 and 0.007, respectively). Linear regression analysis showed significant correlations between HCY concentrations and the severity and extent of atherosclerosis (P=0.0001 for both). In conclusion, hyperhomocysteinemia appears to have a graded effect on the risk of CAD as well as the severity and extent of coronary atherosclerosis. Our findings do not support the homozygous genotype of MTHFR as a genetic risk factor for CAD in this Taiwanese population. Perhaps a further study including assessment of vitamin status is needed to better clarify the relationship between MTHFR genotypes and CAD.

Apolipoprotein B and non-high density lipoprotein cholesterol and the risk of coronary heart disease in Chinese

The aim of our study was to compare apolipoprotein B (apoB), non-high density lipoprotein cholesterol (nonHDL-C), low density lipoprotein cholesterol (LDL-C), and other lipid markers as predictors of coronary heart disease (CHD) in Chinese. Overall, 122 individuals developed CHD during a median 13.6 years of follow-up in 3,568 adult participants from a community-based cohort. The multivariate relative risk of CHD in the highest quintile compared with the lowest quintile was 2.74 [95% confidence interval (CI), 1.45–5.19] for apoB, 1.98 (95% CI, 1.00–3.92) for nonHDL-C, and 1.86 (95% CI, 1.00–3.49) for LDL-C (all tests for trend, P < 0.05). ApoB also had the highest receiver operator characteristic curve area (0.63; 95% CI, 0.58–0.68) in predicting CHD. When apoB and nonHDL-C were mutually adjusted, only apoB was predictive; the relative risk was 2.80 (95% CI, 1.31–5.96; P = 0.001) compared with 1.09 (95% CI, 0.49–2.40; P = 0.75) for nonHDL-C. Compared with the lowest risk, participants with the highest apoB and total cholesterol/HDL-C had a 3-fold increased risk of developing CHD (relative risk = 3.21; 95% CI, 1.45–7.14). These data provide strong evidence that apoB concentration was a better predictor of CHD than other lipid markers in Chinese.

Effects of menopause on intraindividual changes in serum lipids, blood pressure, and body weight—the Chin-Shan community cardiovascular cohort study

In Taiwan, the Chin-Shan Community Cardiovascular Cohort (CCCC) was assessed prospectively to determine whether the changes in cardiovascular risk factors for women age 45--54 years are due to menopause. The average paired percentage changes that occurred between baseline (1990-1991) and follow-up (4 years later) in fasting serum lipids were compared in three groups of women including groups of 59 and 224 who were pre- and postmenopausal, respectively, and a group of 118 who had spontaneously stopped menstruating. Postmenopausal women had the least gain in body mass index (BMI), whereas, mainly premenopausal women had increased systolic blood pressure (P<0.05). All women had elevated total cholesterol (TC) levels, with the greatest elevation in women transitioning into menopause (P<0.001). Low-density lipoprotein cholesterol (LDL-C) levels increased before and during the transition to menopause, but decreased after menopause (P<0.01). Age had significant association with changes in TC, triglyceride (TG) and LDL-C levels, whereas BMI had significant association with changes in TG, LDL-C, and high-density lipoprotein cholesterol (HDL-C) levels (P<0.05). After controlling for age and BMI, only differences in TC remained significant, with the greatest gain in women who stopped menstruating (12.9%) followed by pre- (6.5%) and postmenopausal women (4.8%). Changes in both systolic and diastolic blood pressures, and TG and HDL-C levels were not significantly different, but HDL-C levels declined between 11.5 and 14.7% in all groups. This study suggests an unfavorable effect of menopause on lipid metabolism, especially on the TC level, which was predominantly elevated during the transition to menopause. The decline of HDL-C is of concern.