PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-24 (24)
 

Clipboard (0)
None

Select a Filter Below

Journals
more »
Year of Publication
Document Types
1.  Effectiveness of Bisphosphonate Analogues and Functional Electrical Stimulation on Attenuating Post-Injury Osteoporosis in Spinal Cord Injury Patients- a Systematic Review and Meta-Analysis 
PLoS ONE  2013;8(11):e81124.
Background
Various pharmacologic and non-pharmacologic approaches have been applied to reduce sublesional bone loss after spinal cord injury (SCI), and the results are inconsistent across the studies. The objective of this meta-analysis was to investigate whether the two most-studied interventions, bisphosphonate analogues and functional electrical stimulation (FES), could effectively decrease bone mineral density (BMD) attenuation and/or restore lost BMD in the SCI population.
Methods
Randomized controlled trials, quasi-experimental studies, and prospective follow-up studies employing bisphosphonates or FES to treat post-SCI osteoporosis were identified in PubMed and Scopus. The primary outcome was the percentage of BMD change from baseline measured by dual-energy X-ray absorptiometry (DEXA) or computed tomography (CT). Data were extracted from four points: the 3rd, 6th, 12th, and 18th month after intervention.
Results
A total of 19 studies were included in the analysis and involved 364 patients and 14 healthy individuals. Acute SCI participants treated with bisphosphonate therapy demonstrated a trend toward less bone loss than participants who received placebos or usual care. A significant difference in BMD decline was noted between both groups at the 3rd and 12th month post-medication. The subgroup analysis failed to show the superiority of intravenous bisphosphonate over oral administration. Regarding FES training, chronic SCI patients had 5.96% (95% CI, 2.08% to 9.84%), 7.21% (95%CI, 1.79% to 12.62%), and 9.56% (95% CI, 2.86% to 16.26%) increases in BMD at the 3rd, 6th, and 12th months post-treatment, respectively. The studies employing FES ≥5 days per week were likely to have better effectiveness than studies using FES ≤3 days per week.
Conclusions
Our meta-analysis indicated bisphosphonate administration early following SCI effectively attenuated sublesional bone loss. FES intervention for chronic SCI patients could significantly increase sublesional BMD near the site of maximal mechanical loading.
doi:10.1371/journal.pone.0081124
PMCID: PMC3838359  PMID: 24278386
2.  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.
doi:10.1136/bmj.f6008
PMCID: PMC3807847  PMID: 24157497
3.  A Taiwanese food frequency questionnaire correlates with plasma docosahexaenoic acid but not with plasma eicosapentaenoic acid levels: questionnaires and plasma biomarkers 
Background
Little evidence is available for the validity of dietary fish and polyunsaturated fatty acid intake derived from interviewer-administered questionnaires and plasma docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentration.
Methods
We estimated the correlation of DHA and EPA intake from both questionnaires and biochemical measurements. Ethnic Chinese adults with a mean (± SD) age of 59.8 (±12.8) years (n = 297) (47% women) who completed a 38-item semi-quantitative food-frequency questionnaire and provided a plasma sample were enrolled. Plasma fatty acids were analyzed by capillary gas chromatography.
Results
The Spearmen rank correlation coefficients between the intake of various types of fish and marine n-3 fatty acids as well as plasma DHA were significant, ranging from 0.20 to 0.33 (P < 0.001). In addition, dietary EPA, C22:5 n-3 and DHA were significantly correlated with the levels of marine n-3 fatty acids and DHA, with the Spearman rank correlation coefficients ranging from 0.26 to 0.35 (P < 0.001). Moreover, compared with those in the lowest fish intake quintile, participants in the highest quintile had a significantly higher DHA level (adjusted mean difference, 0.99 ± 0.10%, test for trend, P < 0.001). Similar patterns between dietary DHA intake and plasma DHA levels were found. However, the association between dietary fish intake and plasma EPA was not significant (test for trend, P = 0.69).
Conclusions
The dietary intakes of fish and of long chain n-3 fatty acids, as determined by the food frequency questionnaire, were correlated with the percentages of these fatty acids in plasma, and in particular with plasma DHA. Plasma DHA levels were correlated to dietary intake of long-chain n-3 fatty acids.
doi:10.1186/1471-2288-13-23
PMCID: PMC3598308  PMID: 23414574
N-3 fatty acid; Biomarker; Food frequency questionnaire
4.  Polymorphism of μ-Opioid Receptor Gene (OPRM1:c.118A>G) Might Not Protect against or Enhance Morphine-Induced Nausea or Vomiting 
Pain Research and Treatment  2013;2013:259306.
A cohort, double blind, and randomized study was conducted to investigate the effect of a single nucleotide polymorphism of the μ-opioid receptor at nucleotide position 118 (OPRM1:c.118A>G) on the association with the most common side effects (nausea or vomiting) induced by intravenous patient control analgesia (IVPCA) with morphine, including incidence and severity analysis. A total of 129 Taiwanese women undergoing gynecology surgery received IVPCA with pure morphine for postoperative pain relief. Blood samples were collected and sequenced with high resolution melting analysis to detect three different genotypes of OPRM1 (AA, AG, and GG). All candidates 24 h postoperatively will be interviewed to record the clinical phenotype with subjective complaints and objective observations. The genotyping after laboratory analysis showed that 56 women (43.4%) were AA, 57 (44.2%) were AG, and 16 (12.4%) were GG. The distribution of genotype did not violate Hardy-Weinberg equilibrium test. There was no significant difference neither between the severity and incidence of IVPCA morphine-induced side effects and genotype nor between the association between morphine consumption versus genotype. However, there was significant difference of the relation between morphine consumption and the severity and incidence of IVPCA morphine-induced nausea and vomiting. The genetic analysis for the severity and incidence of IVPCA morphine-induced nausea or vomiting showed no association between phenotype and genotype. It might imply that OPRM1:c.118A>G does not protect against IVPCA morphine-induced nausea or vomiting.
doi:10.1155/2013/259306
PMCID: PMC3575609  PMID: 23431434
5.  Common sequence variants in CD36 gene and the levels of triglyceride and high-density lipoprotein cholesterol among ethnic Chinese in Taiwan 
Background
Evidence of the genetic association between CD36 candidate gene and the risk of metabolic syndrome and its components has been inconsistent. This case–control study assessed the haplotype-tagged SNPs from CD36 on the risk of metabolic syndrome and components.
Methods and results
We recruited 1,000 cases and age, gender-matched controls were randomly selected from the participants with metabolic syndrome defined by International Diabetes Federation. Overall, the haplotype tagged SNPs of CD36 gene were not related to the risk of metabolic syndrome. For individuals with normal lipid levels, several SNPs were significantly associated with the triglycerides and HDL-cholesterol levels: Subjects with rs3211848 homozygote had a higher triglyceride level (99.16 ± 2.61 mg/dL), compared with non-carriers (89.27 ± 1.45 mg/dL, P = 0.001). In addition, compared with non-carriers, individuals with rs1054516 heterozygous and homozygous genotypes had a significantly lower HDL-cholesterol (46.6 ± 0.46 mg/dL for non-carrier, 44.6 ± 0.36 mg/dL for heterozygous, and 44.3 ± 0.56 mg/dL for homozygous, P = 0.0008).
Conclusion
The CD36 gene variants were significantly associated with triglycerides and HDL-cholesterol concentrations among ethnic Chinese in Taiwan.
doi:10.1186/1476-511X-11-174
PMCID: PMC3575328  PMID: 23249574
Metabolic syndrome; CD 36 gene polymorphism
6.  Identification of the HDL-ApoCIII to VLDL-ApoCIII ratio as a predictor of coronary artery disease in the general population: The Chin-Shan Community Cardiovascular Cohort (CCCC) study in Taiwan 
Background
Apolipoprotein (Apo) levels are considered more reliable than plasma lipoprotein levels for predicting coronary artery disease (CAD). However, a unanimous Apo marker for CAD has not been identified. In the Chin-Shan Community Cardiovascular Cohort (CCCC), we sought to identify a common Apo marker for predicting CAD in the general population.
Methods
We examined the cross-sectional association between Apo markers and CAD in the CCCC from 1990 to 2001. Among 3,602 subjects, 90 had angiographically proven CAD (>50% stenosis in ≥1 vessel), and 200 did not have CAD. These subjects were divided into the following 4 groups for analysis: normolipidemic (total cholesterol [TC] <200 mg/dL, triglyceride [TG] <150 mg/dL), hypertriglyceridemic (TC <200 mg/dL, TG ≥150 mg/dL), hypercholesterolemic (TC ≥200 mg/dL, TG <150 mg/dL), and hyperlipidemic (TC ≥200 mg/dL, TG ≥150 mg/dL).
Results
Compatible with findings in other populations, our results showed that CAD patients in the CCCC had higher ApoB and lower high-density lipoprotein (HDL) cholesterol and ApoAI concentrations than non-CAD subjects, but the differences were not significant in all groups. Plasma concentrations of ApoE and lipoprotein (a) were not consistently correlated with CAD. In contrast, the ratio of HDL-ApoCIII to very-low-density lipoprotein (VLDL)-ApoCIII was the only universal determinant for CAD in the normolipidemic group (P=0.0018), the hypertriglyceridemic group (P=0.0001), the hypercholesterolemic group (P=0.0001), and the hyperlipidemic group (P=0.0001). Overall, a high HDL-ApoCIII/VLDL-ApoCIII ratio was observed in all CAD patients, including those with a normal lipid profile. In multivariate analyses, the HDL-ApoCIII/VLDL-ApoCIII ratio was the strongest predictor for CAD among all lipid factors investigated (odds ratio, 2.04; 95% confidence interval, 1.46–2.84; P<0.0001).
Conclusions
A high HDL-ApoCIII to VLDL-ApoCIII ratio is a better marker for predicting CAD than are the conventional lipid markers or ApoAI and ApoB. High HDL-ApoCIII and low VLDL-ApoCIII values in CAD, irrespective of lipid variations, suggest that ApoCIII is markedly transported from VLDL to HDL in this disease. Measurement of plasma ApoCIII may improve CAD prediction in the general population.
doi:10.1186/1476-511X-11-162
PMCID: PMC3543287  PMID: 23173569
Apolipoproteins; Coronary artery disease; Lipoproteins; Cardiovascular risk factors; Chin-Shan Community Cardiovascular Cohort (CCCC) Study; High-density lipoprotein (HDL); Very-low-density lipoprotein (VLDL); Apolipoprotein CIII (ApoCIII)
7.  Differential effects of the changes of LDL cholesterol and systolic blood pressure on the risk of carotid artery atherosclerosis 
Background
The effects of baseline and changes in blood pressure and low density lipoprotein (LDL) cholesterol on the carotid intima media thickness (IMT) have not been well documented.
Methods
A total of 2572 adults (mean age 53.8 years, 54.6% women) in a Taiwanese community undertook three blood pressure and LDL cholesterol examinations over 6 years. Latent growth curve modeling was used to investigate the effects of baseline and change in blood pressure and LDL cholesterol on IMT.
Results
Greater baseline LDL and blood pressure were associated with an increase in IMT (0.005 ± 0.002 mm per 1 mg/dL [p = 0.006] and 0.041 ± 0.004 mm mmHg [p <0.0001], respectively. Change in blood pressure was associated with a significant increase in IMT (0.047±0.016, P = 0.004), whilst the association between change in LDL and change in IMT was not statistically significant (0.008±0.006, P = 0.20).
Conclusions
Carotid IMT was associated with baseline blood pressure and LDL cholesterol, yet only changes of blood pressure, not LDL cholesterol, were related to carotid IMT during the 6-year observation.
doi:10.1186/1471-2261-12-66
PMCID: PMC3445849  PMID: 22900906
Latent growth curve modeling; Carotid intima media thickness; Blood pressure; LDL cholesterol
8.  Lipid-related residual risk and renal function for occurrence and prognosis among patients with first-event acute coronary syndrome and normal LDL cholesterol 
Background
We investigated relationship of low levels of high density lipoprotein cholesterol (HDL-C), high levels of triglycerides, and renal function for the odds, prognosis and survival following acute coronary events among patients with a first event and normal low density lipoprotein cholesterol levels.
Results
A case-control study based on 557 patients and 1086 matched control subjects was conducted. Case patients were followed up for survival with a median of 1.9 years. Participants in the higher quintiles of HDL-C had lower odds to develop acute coronary events (the adjusted odds ratios were 0.24 for the second, 0.24 for the third, 0.10 for the fourth and 0.05 for the fifth quintile). Patients with normal glomerular filtration rate were at a lower risk for all-cause death. However, a reverse association between triglycerides and death risk was found: patients with higher triglycerides were at a lower risk for all-cause death (adjusted relative risk, 0.38 for triglycerides ranging from 82 to 132.9 mg/dL, and 0.14 for triglycerides > = 133 mg/dL).
Conclusions
Low HDL-C was significantly associated with acute coronary events, and triglyceride levels as well as renal function were inversely related to all-cause deaths after the coronary event.
doi:10.1186/1476-511X-10-215
PMCID: PMC3235983  PMID: 22099211
acute coronary syndrome; residual risk; dyslipidemia
9.  The relation of aminoterminal propeptide of type III procollagen and heart rate variability parameters in heart failure patients: A potential serum marker to evaluate cardiac autonomic control and sudden cardiac death 
Background
Cardiac extra-cellular matrix (ECM) fibrosis plays an important role in the pathophysiology of heart failure (HF). It may provide electrical heterogeneity and substrate for arrhythmogenicity, which may cause sudden cardiac death (SCD).
Methods
Twenty-one Patients with HF manifestations, and left ventricular ejection fraction (LVEF) ≤ 50% were enrolled. The median age was 62 years and median LVEF was 33 %. Time- and frequency-domain analysis of heart rate variability (HRV) on 24-hour ambulatory electrocardiography recording was assessed. Serum markers of ECM turnover including type I and III aminoterminal propeptide of procollagen (PINP and PIIINP), matrix metalloproteinase-2 and 9 (MMP-2 and MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) were analyzed.
Results
The serum PIIINP level was significantly correlated with standard deviation of all normal RR intervals (SDNN) (r=−0.722, p=<0.001), percentage of adjacent NN interval differences >50 ms (pNN50) (r=−0.528, p=0.014), percentage of adjacent NN interval differences >20 ms (pNN20) (r=−0.545, p=0.002), very low frequency (VLF) (r=−0.490, p=0.024), low frequency (LF) (r=−0.491, p=0.024), high frequency (HF) (r=−0.513, p=0.018). PINP, MMP-2, 9, TIMP-1 were not correlated with time- and frequency-domain analysis of HRV.
Conclusions
PIIINP was significantly correlated with time- and frequency-domain analysis of HRV in HF patients. PIIINP is a potential serological marker to evaluate cardiac autonomic control and risk of SCD in HF patients.
doi:10.1515/CCLM.2010.348
PMCID: PMC3141296  PMID: 20846104
extra-cellular matrix; heart failure; collagen; HRV
10.  Unravelling the effects of age, period and cohort on metabolic syndrome components in a Taiwanese population using partial least squares regression 
Background
We investigate whether the changing environment caused by rapid economic growth yielded differential effects for successive Taiwanese generations on 8 components of metabolic syndrome (MetS): body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), triglycerides (TG), high-density lipoprotein (HDL), Low-density lipoproteins (LDL) and uric acid (UA).
Methods
To assess the impact of age, birth year and year of examination on MetS components, we used partial least squares regression to analyze data collected by Mei-Jaw clinics in Taiwan in years 1996 and 2006. Confounders, such as the number of years in formal education, alcohol intake, smoking history status, and betel-nut chewing were adjusted for.
Results
As the age of individuals increased, the values of components generally increased except for UA. Men born after 1970 had lower FPG, lower BMI, lower DBP, lower TG, Lower LDL and greater HDL; women born after 1970 had lower BMI, lower DBP, lower TG, Lower LDL and greater HDL and UA. There is a similar pattern between the trend in levels of metabolic syndrome components against birth year of birth and economic growth in Taiwan.
Conclusions
We found cohort effects in some MetS components, suggesting associations between the changing environment and health outcomes in later life. This ecological association is worthy of further investigation.
doi:10.1186/1471-2288-11-82
PMCID: PMC3117818  PMID: 21619595
Metabolic syndrome; obesity; age-period-cohort analysis; partial least squares; Taiwan
11.  Plasma fatty acids and the risk of metabolic syndrome in ethnic Chinese adults in Taiwan 
Background
Evidence of predictive power of various fatty acids on the risk of metabolic syndrome was scanty. We evaluated the role of various fatty acids, including saturated fat, monounsaturated fat, transfat, n-6 fatty acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for the risk of the metabolic syndrome in Taiwan.
Results
A nested case-control study based on 1000 cases of metabolic syndrome and 1:1 matched control subjects. For saturated fat, monounsaturated fat and transfat, the higher the concentration the higher the risk for metabolic syndrome: participants in the highest quintile had a 2.22-fold (95% confidence interval [CI], 1.66 to 2.97) higher risk of metabolic syndrome. In addition, the participants in higher EPA quintiles were less likely to have the risk of metabolic syndrome (adjusted risk, 0.46 [0.34 to 0.61] for the fifth quintile). Participants in the highest risk group (low EPA and high transfat) had a 2.36-fold higher risk of metabolic syndrome (95% CI, 1.38 to 4.03), compared with those in the lowest risk group (high EPA and low transfat). For prediction power, the area under ROC curves increased from 0.926 in the baseline model to 0.928 after adding fatty acids. The net reclassification improvement for metabolic syndrome risk was substantial for saturated fat (2.1%, P = 0.05).
Conclusions
Plasma fatty acid components improved the prediction of the metabolic syndrome risk in Taiwan.
doi:10.1186/1476-511X-10-33
PMCID: PMC3056817  PMID: 21333029
12.  Prediction model for high glycated hemoglobin concentration among ethnic Chinese in Taiwan 
Background
This study aimed to construct a prediction model to identify subjects with high glycated hemoglobin (HbA1c) levels by incorporating anthropometric, lifestyle, clinical, and biochemical information in a large cross-sectional ethnic Chinese population in Taiwan from a health checkup center.
Methods
The prediction model was derived from multivariate logistic regression, and we evaluated the performance of the model in identifying the cases with high HbA1c levels (> = 7.0%). In total 17,773 participants (age > = 30 years) were recruited and 323 participants (1.8%) had high HbA1c levels. The study population was divided randomly into two parts, with 80% as the derivation data and 20% as the validation data.
Results
The point-based clinical model, including age (maximal 8 points), sex (1 point), family history (3 points), body mass index (2 points), waist circumference (4 points), and systolic blood pressure (3 points) reached an area under the receiver operating characteristic curve (AUC) of 0.723 (95% confidence interval, 0.677- 0.769) in the validation data. Adding biochemical measures such as triglycerides and HDL cholesterol improved the prediction power (AUC, 0.770 [0.723 - 0.817], P = < 0.001 compared with the clinical model). A cutoff point of 7 had a sensitivity of 0.76 to 0.96 and a specificity of 0.39 to 0.63 for the prediction model.
Conclusions
A prediction model was constructed for the prevalent risk of high HbA1c, which could be useful in identifying high risk subjects for diabetes among ethnic Chinese in Taiwan.
doi:10.1186/1475-2840-9-59
PMCID: PMC2955643  PMID: 20875098
13.  Postprandial Glucose Improves the Risk Prediction of Cardiovascular Death Beyond the Metabolic Syndrome in the Nondiabetic Population 
Diabetes Care  2009;32(9):1721-1726.
OBJECTIVE
With increasing evidence about the cardiovascular risk associated with postprandial nonfasting glucose and lipid dysmetabolism, it remains uncertain whether the postprandial glucose concentration increases the ability of metabolic syndrome to predict cardiovascular events.
RESEARCH DESIGN AND METHODS
This was an observational study of 15,145 individuals aged 35–75 years without diabetes or cardiovascular diseases. Postprandial glucose was obtained 2 h after a lunch meal. Metabolic syndrome was diagnosed using the criteria of the U.S. National Cholesterol Education Program Adult Treatment Panel III. Cardiovascular and all-cause deaths were primary outcomes.
RESULTS
During a median follow-up of 6.7 years, 410 individuals died, including 82 deaths from cardiovascular causes. In a Cox model adjusting for metabolic syndrome status as well as age, sex, smoking, systolic blood pressure, LDL, and HDL cholesterol levels, elevated 2-h postprandial glucose increased the risk of cardiovascular and all-cause death (per millimole per liter increase, hazard ratio 1.26 [95% CI 1.11–1.42] and 1.10 [1.04–1.16], respectively), with significant trends across the postprandial glucose quintiles. Including 2-h postprandial glucose into a metabolic syndrome–included multivariate risk prediction model conferred a discernible improvement of the model in discriminating between those who died of cardiovascular causes and who did not (integrated discrimination improvement 0.4, P = 0.005; net reclassification improvement 13.4%, P = 0.03); however, the improvement was only marginal for all-cause death.
CONCLUSIONS
Given the risk prediction based on metabolic syndrome and established cardiovascular risk factors, 2-h postprandial glucose improves the predictive ability to identity nondiabetic individuals at increased risk of cardiovascular death.
doi:10.2337/dc08-2337
PMCID: PMC2732157  PMID: 19502543
14.  Evaluation of the diagnostic performance of infrared imaging of the breast: a preliminary study 
Background
The study was conducted to investigate the diagnostic performance of infrared (IR) imaging of the breast using an interpretive model derived from a scoring system.
Methods
The study was approved by the Institutional Review Board of our hospital. A total of 276 women (mean age = 50.8 years, SD 11.8) with suspicious findings on mammograms or ultrasound received IR imaging of the breast before excisional biopsy. The interpreting radiologists scored the lesions using a scoring system that combines five IR signs. The ROC (receiver operating characteristic) curve and AUC (area under the ROC curve) were analyzed by the univariate logistic regression model for each IR sign and an age-adjusted multivariate logistic regression model including 5 IR signs. The cut-off values and corresponding sensitivity, specificity, Youden's Index (Index = sensitivity+specificity-1), positive predictive value (PPV), negative predictive value (NPV) were estimated from the age-adjusted multivariate model. The most optimal cut-off value was determined by the one with highest Youden's Index.
Results
For the univariate model, the AUC of the ROC curve from five IR signs ranged from 0.557 to 0.701, and the AUC of the ROC from the age-adjusted multivariate model was 0.828. From the ROC derived from the multivariate model, the sensitivity of the most optimal cut-off value would be 72.4% with the corresponding specificity 76.6% (Youden's Index = 0.49), PPV 81.3% and NPV 66.4%.
Conclusions
We established an interpretive age-adjusted multivariate model for IR imaging of the breast. The cut-off values and the corresponding sensitivity and specificity can be inferred from the model in a subpopulation for diagnostic purpose.
Trial Registration
NCT00166998.
doi:10.1186/1475-925X-9-3
PMCID: PMC2818658  PMID: 20055999
15.  Vitamin C supplementation does not protect L-gulono-γ-lactone oxidase-deficient mice from Helicobacter pylori-induced gastritis and gastric premalignancy 
In human studies, low vitamin C intake has been associated with more severe Helicobacter pylori gastritis and a higher incidence of gastric cancer. However, vitamin C supplementation has not been definitively shown to protect against gastric cancer. Using vitamin C-deficient B6.129P2-Gulotm1Umc/mmcd (gulo−/−) mice lacking L-gulono-γ-lactone oxidase, we compared gastric lesions and Th1 immune responses in H. pylori-infected gulo−/− mice supplemented with low (33 mg/L) or high (3,300 mg/L) vitamin C in drinking water for 16 or 32 weeks. Vitamin C levels in plasma and gastric tissue correlated with the vitamin C supplementation levels in gulo−/− mice. H. pylori infection resulted in comparable gastritis and premalignant lesions in wildtype C57BL/6 and gulo−/− mice supplemented with high vitamin C, but lesions were less severe in gulo−/− mice supplemented with low vitamin C at 32 weeks post infection. The reduced gastric lesions in infected gulo−/− mice supplemented with low vitamin C correlated with reduced Th1-associated IgG2c, gastric IFN-γ and TNF-α mRNA and higher H. pylori colonization levels. These results in the H. pylori-infected gulo−/− mouse model suggest that although supplementation with a high level of vitamin C achieved physiologically normal vitamin C levels in plasma and gastric tissue, this dose of vitamin C did not protect gulo−/− mice from H. pylori-induced premalignant gastric lesions. In addition, less severe gastric lesions in H. pylori infected gulo−/− mice supplemented with low vitamin C correlated with an attenuated Th1 inflammatory response.
doi:10.1002/ijc.23228
PMCID: PMC2766771  PMID: 17990318
Helicobacter pylori; vitamin C; gulo−/− mouse model
16.  Carotid Artery Intima-Media Thickness, Carotid Plaque and Coronary Heart Disease and Stroke in Chinese 
PLoS ONE  2008;3(10):e3435.
Background
Our aim was to prospectively investigate the association between carotid artery intima-media thickness (IMT) as well as carotid plaque and incidence of coronary heart disease (CHD) and stroke in Chinese, among whom data are limited.
Methods and Findings
We conducted a community-based cohort study composed of 2190 participants free of cardiovascular disease at baseline in one community. During a median 10.5-year follow up, we documented 68 new cases of coronary heart disease and 94 cases of stroke. The multivariate relative risks (RRs) associated with a change of 1 standard deviation of maximal common carotid IMT were 1.38 (95% confidence interval [CI], 1.12–1.70) for CHD and 1.47 (95% CI, 1.28–1.69) for stroke. The corresponding RRs with internal carotid IMT were 1.47 (95% CI, 1.21–1.79) for CHD and 1.52 (95% CI, 1.31–1.76) for stroke. Carotid plaque measured by the degree of diameter stenosis was also significantly associated with increased risk of CHD (p for trend<0.0001) and stroke (p for trend<0.0001). However, these associations were largely attenuated when adjusting for IMT measurements.
Conclusions
This prospective study indicates a significant association between carotid IMT and incidence of CHD and stroke in Chinese adults. These measurements may be useful for cardiovascular risk assessment and stratification in Chinese.
doi:10.1371/journal.pone.0003435
PMCID: PMC2562458  PMID: 18927612
17.  Heritability and major gene effects on left ventricular mass in the Chinese population: a family study 
Background
Genetic components controlling for echocardiographically determined left ventricular (LV) mass are still unclear in the Chinese population.
Methods
We conducted a family study from the Chin-San community, Taiwan, and a total of 368 families, 1145 subjects, were recruited to undergo echocardiography to measure LV mass. Commingling analysis, familial correlation, and complex segregation analysis were applied to detect component distributions and the mode of inheritance.
Results
The two-component distribution model was the best-fitting model to describe the distribution of LV mass. The highest familial correlation coefficients were mother-son (0.379, P < .0001) and father-son (0.356, P < .0001). Genetic heritability (h2) of LV mass was estimated as 0.268 ± 0.061 (P < .0001); it decreased to 0.153 ± 0.052 (P = .0009) after systolic blood pressure adjustment. Major gene effects with polygenic components were the best-fitting model to explain the inheritance mode of LV mass. The estimated allele frequency of the gene was 0.089.
Conclusion
There were significant familial correlations, heritability and a major gene effect on LV mass in the population-based families.
doi:10.1186/1471-2261-6-37
PMCID: PMC1579230  PMID: 16945138
18.  Interaction of obesity, metabolic syndrome and Framingham risk on steatohepatitis among healthy Taiwanese: population-based nested case-control study 
Background
There have been scant reports on the cumulative effects of atherosclerotic risk factors on steatohepatitis.
Methods
We defined cases of steatohepatitis (n = 124) from one health examination center at National Taiwan University Hospital from January to December 2002. We selected controls, matched by age, gender and drinking status. Metabolic syndrome was defined by the modified ATP-III guidelines. High-dimensional interactions of risk factors for steatohepatitis were evaluated.
Results
Steatohepatitis cases had the highest C-reactive protein, lymphocytes, Framingham scores and predicted coronary risks. The odds ratio (OR) of metabolic syndrome for steatohepatitis was the highest (OR = 9.9), followed by high glucose status (OR = 4.5) and obesity (OR = 3.6). The highest area under the ROC curve was metabolic syndrome (area = 0.80), followed by obesity (0.75) and high glucose level (0.73). Metabolic syndrome was the highest population-attributable risk factor (0.59). Significant interaction was found with a three-factor model, including obesity, metabolic syndrome and Framingham risk status, with lesser average prediction error (22.6%), higher average cross-validation consistency (6.3) and lower average prediction error (24.3%). Compared with persons with no risk factors, OR increased as the number of risk factors increased (OR = 3.0 with one risk factor, 17.5 with two risk factors, 10.8 with three risk factors, respectively).
Conclusion
Metabolic syndrome, inflammation markers and atherosclerotic risk scores are significantly related to steatohepatitis status among the healthy examinee population in Taiwan.
doi:10.1186/1475-2840-5-12
PMCID: PMC1481540  PMID: 16707022
19.  Treatment of low back pain by acupressure and physical therapy: randomised controlled trial 
BMJ : British Medical Journal  2006;332(7543):696-700.
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.
doi:10.1136/bmj.38744.672616.AE
PMCID: PMC1410852  PMID: 16488895
20.  Segregation analysis of apolipoprotein A1 levels in families of adolescents: A community-based study in Taiwan 
BMC Genetics  2006;7:4.
Background
Apolipoprotein (Apo) A1 is a protective factor for cardiovascular events. This study aimed to perform complex segregation analyses of Apo A1 levels in families of adolescents systematically ascertained from the junior high school students in a rural community. Both siblings and parents of the adolescent probands were recruited for the study. Apo A1 concentrations were measured by turbidimetric immunoassay methods. After adjustment for gender, age, body mass index, smoking and drinking status, residual values of Apo A1 were subjected to subsequent analyses.
Results
Significant mother-father and parent-offspring correlations were found. Commingling analyses indicated that a four-component distribution model was needed to account for the Apo A1 variation. Segregation analysis using regressive models revealed that the best-fit model of Apo A1 was a model of environmental effect plus familial correlation (heritability = 23.9%), in which a significant mother-father correlation existed. Models containing major gene effect could be rejected.
Conclusion
These results suggest that variations of Apo A1 levels in the normal range, especially during adolescence, are likely to be influenced by multiple factors without significant contribution from major genes.
doi:10.1186/1471-2156-7-4
PMCID: PMC1360683  PMID: 16423305
21.  Bioavailability study of fixed-dose tablet versus capsule formulation of amlodipine plus benazepril: A randomized, single-dose, two-sequence, two-period, open-label, crossover study in healthy volunteers 
Background:
In the treatment of hypertension, combination therapy is important10 because antihypertensive monotherapy is effective in only 40% of patients worldwide. Amlodipine is a dihydropyridine calcium channel blocker with a slow onset and long duration of action. Benazepril hydrochloride is a prodrug hydrolyzed by esterase to the active metabolite benazeprilat, an angiotensin-converting enzyme inhibitor. In 1995, the US Food and Drug Administration approved the use of a capsule formulation of combination amlodipine-benazepril for hypertension.
Objective:
The aim of this study was to compare the bioavailability and tolerability10 of the capsule formulation with those of a tablet formulation of combination amlodipine-benazepril in healthy volunteers.
Methods:
This single-dose, 2-sequence, 2-period, open-label, crossover10 study recruited healthy, adult, male volunteers with normotension. Subjects were randomly assigned to 1 of 2 treatment sequences: a single-dose tablet containing amlodipine 5 mg plus benazepril 10 mg, followed by a single-dose capsule containing the same dose of each drug (AB), or vice versa (BA). The treatment period for each drug consisted of dosing and pharmacokinetic analysis on day 1, followed by pharmacokinetic analysis on days 2 to 7. Treatment periods were separated by a 4-week washout period. For pharmacokinetic analysis, serial blood samples were obtained before dosing and at 20, 40, 60, 80, and 100 minutes and 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 60, 84, 108, 132, and 156 hours after dosing. Tolerability was assessed using subject interview and spontaneous reporting.
Results:
Twelve healthy, male, Taiwanese subjects (mean [SD] age, 23.510 [1.7] years) participated in the study. No statistically significant differences inbioavailability were found between the 2 formulations based on the pharmacokinetic measurements of amlodipine and benazeprilat. The rate and extent of absorption of the tablets were found to be comparable to those of the capsules (90% CI, between 80% and 125%). The mean (SD) relative bioavailabilities, as represented by AUC0−∞, of amlodipine and benazeprilat for tablets versus capsules were 1.060 (0.170) versus 0.949 (0.197), respectively. The mean plasma concentration-time profiles of amlodipine and benazeprilat were graphically similar. No adverse effects were observed with either formulation.
Conclusions:
The results of this bioavailability comparison study in this 10 population of healthy, male, Taiwanese volunteers suggest that the tablet and capsule formulations of combination amlodipine-benazepril are bioequivalent. Both formulations were well tolerated.
doi:10.1016/j.curtheres.2005.04.005
PMCID: PMC3964558
bioequivalence; bioavailability; pharmacokinetics; amlodipinebesylate; benazepril hydrochloride; fixed-dose combination
22.  Sibling recurrence risk ratio analysis of the metabolic syndrome and its components over time 
BMC Genetics  2003;4(Suppl 1):S33.
Background
The purpose of this study was to estimate both cross-sectional sibling recurrence risk ratio (λs) and lifetime λs for the metabolic syndrome and its individual components over time among sibships in the prospectively followed-up cohorts provided by the Genetic Analysis Workshop 13. Five measures included in the operational criteria of the metabolic syndrome by the Adult Treatment Panel III were examined. A method for estimating sibling recurrence risk with correction for complete ascertainment was used to estimate the numerator, and the prevalence in the whole cohort was used as the denominator of λs.
Results
Considerable variability in the λs was found in terms of different time-points for the cross-sectional definition, the times of fulfilling the criterion for lifetime definition, and different components. Obesity and hyperglycemia had the highest cross-sectional λs of the five components. Both components also had the largest slopes in the linear trend of the lifetime λs. However, the magnitudes of the lifetime λs were similar to that of the mean cross-sectional λs, which were <2. The results of nonparametric linkage analysis showed only suggestive evidence of linkage between one marker and lifetime diagnosis of low high-density lipoprotein cholesterol and metabolic syndrome, respectively.
Conclusion
The λs of the metabolic syndrome and its components varies substantially across time, and the λs of lifetime diagnosis was not necessarily larger than that of a cross-sectional diagnosis. The magnitude of λs does not predict well the maximum LOD score of linkage analysis.
doi:10.1186/1471-2156-4-S1-S33
PMCID: PMC1866469  PMID: 14975101
23.  Consistency of genetic inheritance mode and heritability patterns of triglyceride vs. high density lipoprotein cholesterol ratio in two Taiwanese family samples 
BMC Genetics  2003;4:7.
Background
Triglyceride/HDL cholesterol ratio (TG/HDL-C) is considered as a risk factor for cardiovascular events. Genetic components were important in controlling the variation in western countries. But the mode of inheritance and family aggregation patterns were still unknown among Asian-Pacific countries. This study, based on families recruited from community and hospital, is aimed to investigate the mode of inheritance, heritability and shared environmental factors in controlling TG/HDL-C.
Results
Two populations, one from community-based families (n = 988, 894 parent-offspring and 453 sibling pairs) and the other from hospital-based families (n = 1313, 76 parent-offspring and 52 sibling pairs) were sampled. The population in hospital-based families had higher mean age values than community-based families (54.7 vs. 34.0). Logarithmic transformed TG/ HDL-C values, after adjusted by age, gender and body mass index, were for genetic analyses. Significant parent-offspring and sibling correlations were also found in both samples. The parent-offspring correlation coefficient was higher in the hospital-based families than in the community-based families. Genetic heritability was higher in community-based families (0.338 ± 0.114, p = 0.002), but the common shared environmental factor was higher in hospital-based families (0.203 ± 0.042, p < 0.001). Commingling analyses showed that more than one-component distribution models were the best-fit models to explain the variance in both populations. Complex segregation analysis by regressive models revealed that in both samples the best-fit model of TG/HDL-C was the model of environmental effects plus familial correlation, in which significant parent-offspring and sibling correlations were demonstrated. Models of major gene effects were rejected in both samples.
Conclusion
Variations of TG/HDL-C in the normal ranges were likely to be influenced by multiple factors, including environmental and genetic components. Higher genetic factors were proved in younger community-based families than in older hospital-based families.
doi:10.1186/1471-2156-4-7
PMCID: PMC155683  PMID: 12710891
24.  Pitavastatin and Atorvastatin Double-Blind Randomized ComPArative Study among HiGh-Risk Patients, Including ThOse with Type 2 Diabetes Mellitus, in Taiwan (PAPAGO-T Study) 
PLoS ONE  2013;8(10):e76298.
Background
Evidence about the efficacy and safety of statin treatment in high-risk patients with hypercholesterolemia is available for some populations, but not for ethnic Chinese. To test the hypothesis that treatment with pitavastatin (2 mg/day) is not inferior to treatment with atorvastatin (10 mg/day) for reducing low-density lipoprotein cholesterol (LDL-C), a 12-week multicenter collaborative randomized parallel-group comparative study of high-risk ethnic Chinese patients with hypercholesterolemia was conducted in Taiwan. In addition, the effects on other lipid parameters, inflammatory markers, insulin-resistance-associated biomarkers and safety were evaluated.
Methods and Results
Between July 2011 and April 2012, 251 patients were screened, 225 (mean age: 58.7 ± 8.6; women 38.2% [86/225]) were randomized and treated with pitavastatin (n = 112) or atorvastatin (n = 113) for 12 weeks. Baseline characteristics in both groups were similar, but after 12 weeks of treatment, LDL-C levels were significantly lower: pitavastatin group = −35.0 ± 14.1% and atorvastatin group = −38.4 ± 12.8% (both: p < 0.001). For the subgroup with diabetes mellitus (DM) (n = 125), LDL-C levels (−37.1 ± 12.9% vs. −38.0 ± 13.1%, p = 0.62) were similarly lowered after either pitavastatin (n = 63) or atorvastatin (n = 62) treatment. Triglycerides, non-high density lipoprotein cholesterol, and apoprotein B were similarly and significantly lower in both treatment groups. In non-lipid profiles, HOMA-IR and insulin levels were higher to a similar degree in both statin groups. Hemoglobin A1C was significantly (p = 0.001) higher in the atorvastatin group but not in the pitavastatin group. Both statins were well tolerated, and both groups had a similar low incidence of treatment-emergent adverse events.
Conclusion
Both pitavastatin (2 mg/day) and atorvastatin (10 mg/day) were well tolerated, lowered LDL-C, and improved the lipid profile to a comparable degree in high-risk Taiwanese patients with hypercholesterolemia.
Trial Registration
ClinicalTrials.gov NCT01386853 http://clinicaltrials.gov/ct2/show/NCT01386853?term=NCT01386853&rank=1
doi:10.1371/journal.pone.0076298
PMCID: PMC3788128  PMID: 24098467

Results 1-24 (24)